International Journal of Medical Sciences
Title: MALAT1 As A Diagnostic and Therapeutic Target in Diabetes-Related Complications: A Promising Long-Noncoding RNAAuthor List1.# Leila Elmi Abdulle, M.D.Department of Ophthalmology, the First Hospital of Jilin University, No. 71 of Xinmin St.Changchun, Jilin Province, 130021, China. Email address: leilabdulle@2. # Ji-long Hao M.D., Ph.D.Department of Ophthalmology, the First Hospital of Jilin University, No. 71 of Xinmin St. Changchun, Jilin Province, 130021, China. Email address: 289736582@3. # Om Prakash Pant, M.D.Department of Ophthalmology, the First Hospital of Jilin University, No. 71 of Xinmin St. Changchun, Jilin Province, 130021, China. Email address: ompant201@4. # Xiu-fen Liu, M.D., Ph.D.Department of Ophthalmology, the First Hospital of Jilin University, No. 71 of Xinmin St. Changchun, Jilin Province, 130021, China. Email address: xiufenliu16@5. # Dan-dan Zhou, M.D., Ph.D.Department of Radiology, The First Hospital of Jilin University, No. 71 of Xinmin St. Changchun, Jilin Province, 130021, China Email address: zhoudan0928@6. # Ying-Gao, M.D., Ph.D.Department of Endocrinology, The First Hospital of Jilin University, No. 71 of Xinmin St. Changchun, Jilin Province, 130021, China Email address: gaoyingcc@7. #Abhishek Suwal, M.D.Department of Ophthalmology, the First Hospital of Jilin University, No. 71 of Xinmin St. Changchun, Jilin Province, 130021, China. Email address: abhisheksuwal@ 8.*Cheng-wei Lu, M.D., Ph.D.Department of Ophthalmology, the First Hospital of Jilin University, No. 71 of Xinmin St. Changchun, Jilin Province, 130021, China. Email address: lcwchina800@# Leila Elmi Abdulle, Ji-long Hao, Om Prakash Pant, Xiu-fen Liu, Dan-Dan Zhou, Ying-Gao and Abhishek Suwal are co-first authors.*Corresponding author:Cheng-wei Lu, M.D., Ph.D.Department of Ophthalmology, the First Hospital of Jilin University, No. 71 of Xinmin St. Changchun, Jilin Province, 130021, China. Email address: lcwchina800@ Telephone No: +8618684317115.AbstractDiabetes mellitus is a global issue with increasing incidence rate worldwide. In an uncontrolled case, it can advance to various organ-related complications leading to an increase in morbidity and mortality. Long non-coding RNA (lncRNA) Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) appears to be a fairly novel lncRNA that is relevant to diabetes and its role in diabetic-related diseases initiation and progression have long been a subject of attention to many scholars. The expression of MALAT1 is elevated in different diabetic-related diseases. In this review, we demonstrate the various functions of MALAT1 in the different diabetes-related complications including ischemic reperfusion injury, retinopathy, cataract, atherosclerosis, cardiomyopathy, non-alcoholic steatohepatitis, gastroparesis, kidney disease, and gestational diabetes. The emerging evidence showed that the role of MALAT1 in diabetic-related complications is both pro-inflammatory and apoptosis in different cell types. These results concluded that MALAT1 is a potential diagnostic and future targeted therapy for diabetes-associated complications. Keywords: Diabetes mellitus; Diabetes-related complications; Long non-coding RNA; MALAT1.IntroductionDiabetes mellitus (DM) is a clinical condition characterized by a high glucose level either due to decreased insulin level or due to insulin insensitivity ADDIN EN.CITE <EndNote><Cite><Author>Guay</Author><Year>2013</Year><RecNum>1</RecNum><DisplayText>[1]</DisplayText><record><rec-number>1</rec-number><foreign-keys><key app="EN" db-id="ftefxe9rma55d4ewzvmpseva9s2zwaassrra" timestamp="0">1</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Guay, C.</author><author>Regazzi, R.</author></authors></contributors><auth-address>University of Lausanne, Department of Fundamental Neurosciences, Rue du Bugnon 9, 1005 Lausanne, Switzerland.</auth-address><titles><title>Circulating microRNAs as novel biomarkers for diabetes mellitus</title><secondary-title>Nat Rev Endocrinol</secondary-title><alt-title>Nature reviews. Endocrinology</alt-title></titles><pages>513-21</pages><volume>9</volume><number>9</number><keywords><keyword>Diabetes Mellitus, Type 1/*blood/genetics/pathology</keyword><keyword>Diabetes Mellitus, Type 2/*blood/genetics/pathology</keyword><keyword>Humans</keyword><keyword>MicroRNAs/*blood</keyword></keywords><dates><year>2013</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>1759-5037 (Electronic)
1759-5029 (Linking)</isbn><accession-num>23629540</accession-num><urls><related-urls><url>;[1]. The International Diabetes Federation (IDF) estimated on the overall prevalence of DM to be 366 million in 2011, and it is predicted to rise to 552 million by 2030 ADDIN EN.CITE <EndNote><Cite><Author>Whiting</Author><Year>2011</Year><RecNum>2</RecNum><DisplayText>[2]</DisplayText><record><rec-number>2</rec-number><foreign-keys><key app="EN" db-id="ftefxe9rma55d4ewzvmpseva9s2zwaassrra" timestamp="0">2</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Whiting, D. R.</author><author>Guariguata, L.</author><author>Weil, C.</author><author>Shaw, J.</author></authors></contributors><auth-address>International Diabetes Federation, Brussels, Belgium. david@davidwhiting.me.uk</auth-address><titles><title>IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030</title><secondary-title>Diabetes Res Clin Pract</secondary-title><alt-title>Diabetes research and clinical practice</alt-title></titles><pages>311-21</pages><volume>94</volume><number>3</number><keywords><keyword>Diabetes Mellitus/*epidemiology</keyword><keyword>*Global Health</keyword><keyword>Humans</keyword><keyword>Models, Statistical</keyword><keyword>Prevalence</keyword><keyword>Time Factors</keyword><keyword>World Health Organization</keyword></keywords><dates><year>2011</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>1872-8227 (Electronic)
0168-8227 (Linking)</isbn><accession-num>22079683</accession-num><urls><related-urls><url>;[2]. In uncontrolled cases, DM can affect various organs including the brain, eye, heart, stomach, kidney and liver leading to various severe and organ-threatening complications PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IYW5lZmVsZDwvQXV0aG9yPjxZZWFyPjIwMTM8L1llYXI+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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IYW5lZmVsZDwvQXV0aG9yPjxZZWFyPjIwMTM8L1llYXI+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ADDIN EN.CITE.DATA [3-5]. Currently, there is no specific biomarker for diabetes complicated diseases as well as treatment regimens that could halt and prevent the disease progression. Hence it is urgent to explore the specific biomarkers to diagnose, detect, and catch the early sequence of disease development. Long non-coding RNA (lncRNA) are well-defined enormous and different class of transcribed RNA molecules with dimension of more than 200 nucleotides but lack an open reading structure of considerable size. Similar to the protein-coding RNAs, most of the lncRNA are RNA polymerase II transcripts with a 5 ‘cap and poly-A tail. The majority of lncRNA are predominant inside the cell nucleus and show either low revolutionary conservation or lesser expression level than mRNAs PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5SaW5uPC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48UmVj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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5SaW5uPC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48UmVj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ADDIN EN.CITE.DATA [6, 7]. LncRNA is an important regulator of various biological processes, including proliferation, differentiation, invasion and apoptosis ADDIN EN.CITE <EndNote><Cite><Author>Liu</Author><Year>2018</Year><RecNum>8</RecNum><DisplayText>[8]</DisplayText><record><rec-number>8</rec-number><foreign-keys><key app="EN" db-id="ftefxe9rma55d4ewzvmpseva9s2zwaassrra" timestamp="0">8</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Liu, X. F.</author><author>Hao, J. L.</author><author>Xie, T.</author><author>Pant, O. P.</author><author>Lu, C. B.</author><author>Lu, C. W.</author><author>Zhou, D. D.</author></authors></contributors><auth-address>Department of Ophthalmology, The First Hospital of Jilin University, Jilin, China.
Department of. Neurosurgery, The People's Hospital of Jilin Province, Jilin, China.
Department of Cardiology, The First Hospital of Jiamusi University, Heilongjiang, China.
Department of Radiology, The First Hospital of Jilin University, Jilin, China.</auth-address><titles><title>The BRAF activated non-coding RNA: A pivotal long non-coding RNA in human malignancies</title><secondary-title>Cell Prolif</secondary-title><alt-title>Cell proliferation</alt-title></titles><pages>e12449</pages><volume>51</volume><number>4</number><dates><year>2018</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1365-2184 (Electronic)
0960-7722 (Linking)</isbn><accession-num>29484737</accession-num><urls><related-urls><url>;[8]. Hence, lncRNA are evolving as new biomarkers and therapeutic targets in several human diseases ADDIN EN.CITE <EndNote><Cite><Author>Weidle</Author><Year>2017</Year><RecNum>9</RecNum><DisplayText>[9]</DisplayText><record><rec-number>9</rec-number><foreign-keys><key app="EN" db-id="ftefxe9rma55d4ewzvmpseva9s2zwaassrra" timestamp="0">9</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Weidle, U. H.</author><author>Birzele, F.</author><author>Kollmorgen, G.</author><author>Ruger, R.</author></authors></contributors><auth-address>Roche Innovation Center Munich, Roche Diagnostics GmbH, Penzberg, Germany.
Roche Innovation Center Basel, F. Hofman La Roche, Basel, Switzerland.
Roche Innovation Center Munich, Roche Diagnostics GmbH, Penzberg, Germany ruediger.rueger@.</auth-address><titles><title>Long Non-coding RNAs and their Role in Metastasis</title><secondary-title>Cancer Genomics Proteomics</secondary-title><alt-title>Cancer genomics & proteomics</alt-title></titles><pages>143-160</pages><volume>14</volume><number>3</number><keywords><keyword>Gene Expression Regulation, Neoplastic/genetics</keyword><keyword>Humans</keyword><keyword>Neoplasm Metastasis</keyword><keyword>Neoplasms/*genetics/pathology</keyword><keyword>RNA, Long Noncoding/classification/*genetics</keyword></keywords><dates><year>2017</year><pub-dates><date>May-Jun</date></pub-dates></dates><isbn>1790-6245 (Electronic)
1109-6535 (Linking)</isbn><accession-num>28446530</accession-num><urls><related-urls><url>;[9]. LncRNA-Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is among well studied and highly conserved lncRNA, which was linked to a variety of pathological processes including diabetes-related complications and various malignancies PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TdTwvQXV0aG9yPjxZZWFyPjIwMTY8L1llYXI+PFJlY051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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TdTwvQXV0aG9yPjxZZWFyPjIwMTY8L1llYXI+PFJlY051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ADDIN EN.CITE.DATA [10]. MALAT1 coding gene is located on the short arm of human chromosome 11q13.1, and its transcript is approximately 8 kb ADDIN EN.CITE <EndNote><Cite><Author>Wilusz</Author><Year>2008</Year><RecNum>11</RecNum><DisplayText>[11]</DisplayText><record><rec-number>11</rec-number><foreign-keys><key app="EN" db-id="ftefxe9rma55d4ewzvmpseva9s2zwaassrra" timestamp="0">11</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Wilusz, J. E.</author><author>Freier, S. M.</author><author>Spector, D. L.</author></authors></contributors><auth-address>Watson School of Biological Sciences, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.</auth-address><titles><title>3' end processing of a long nuclear-retained noncoding RNA yields a tRNA-like cytoplasmic RNA</title><secondary-title>Cell</secondary-title><alt-title>Cell</alt-title></titles><pages>919-32</pages><volume>135</volume><number>5</number><keywords><keyword>Amino Acid Sequence</keyword><keyword>Animals</keyword><keyword>Base Sequence</keyword><keyword>Cell Line, Tumor</keyword><keyword>Cell Nucleus/genetics/metabolism</keyword><keyword>Cytoplasm/*metabolism</keyword><keyword>Endoribonucleases/metabolism</keyword><keyword>HeLa Cells</keyword><keyword>Humans</keyword><keyword>Mice</keyword><keyword>Molecular Sequence Data</keyword><keyword>Neoplasms/genetics/metabolism</keyword><keyword>*RNA Processing, Post-Transcriptional</keyword><keyword>RNA, Transfer/genetics/metabolism</keyword><keyword>RNA, Untranslated/genetics/*metabolism</keyword><keyword>Ribonuclease P/metabolism</keyword></keywords><dates><year>2008</year><pub-dates><date>Nov 28</date></pub-dates></dates><isbn>1097-4172 (Electronic)
0092-8674 (Linking)</isbn><accession-num>19041754</accession-num><urls><related-urls><url>;[11]. Recent studies had revealed that MALAT1 can play significant roles in the pathophysiological process, tissue inflammation, tumor progression, angiogenesis, cardiovascular remodelling, liver fibrosis, and diabetes progression by modulating gene transcription ADDIN EN.CITE <EndNote><Cite><Author>Lei</Author><Year>2018</Year><RecNum>12</RecNum><DisplayText>[12]</DisplayText><record><rec-number>12</rec-number><foreign-keys><key app="EN" db-id="ftefxe9rma55d4ewzvmpseva9s2zwaassrra" timestamp="0">12</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lei, L.</author><author>Chen, J.</author><author>Huang, J.</author><author>Lu, J.</author><author>Pei, S.</author><author>Ding, S.</author><author>Kang, L.</author><author>Xiao, R.</author><author>Zeng, Q.</author></authors></contributors><auth-address>Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Department of Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Department of Dermatology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Department of Dermatology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.</auth-address><titles><title>Functions and regulatory mechanisms of metastasis-associated lung adenocarcinoma transcript 1</title><secondary-title>J Cell Physiol</secondary-title><alt-title>Journal of cellular physiology</alt-title></titles><dates><year>2018</year><pub-dates><date>Aug 21</date></pub-dates></dates><isbn>1097-4652 (Electronic)
0021-9541 (Linking)</isbn><accession-num>30132842</accession-num><urls><related-urls><url>;[12]. In this review, we focused on the correlation between MALAT1 and diabetes-related complications and highlighted the currently advanced research evolutions on the different expression pattern of MALAT1, along with the precise biological role in those diseases (Table 1). MALAT1 may act as an innovative biomarker and therapeutic target for the diagnosis and treatment of diabetes-related complications and disease prognosis assessment. Furthermore, MALAT1- targeting therapeutic inventions may be identified as a promising prevention and treatment option for associated diabetic diseases. MALAT1 in Diabetes-Related Complications Cerebral Ischemic Reperfusion Injury Cerebrovascular disease has a high incidence of neurological disorders, disability and mortality that severely depreciate the human health PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYWNraG91c2U8L0F1dGhvcj48WWVhcj4yMDE3PC9ZZWFy
PjxSZWNOdW0+MTM8L1JlY051bT48RGlzcGxheVRleHQ+WzEzXTwvRGlzcGxheVRleHQ+PHJlY29y
ZD48cmVjLW51bWJlcj4xMzwvcmVjLW51bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIg
ZGItaWQ9ImZ0ZWZ4ZTlybWE1NWQ0ZXd6dm1wc2V2YTlzMnp3YWFzc3JyYSIgdGltZXN0YW1wPSIw
Ij4xMzwva2V5PjwvZm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJKb3VybmFsIEFydGljbGUi
PjE3PC9yZWYtdHlwZT48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+QmFja2hvdXNlLCBF
LiBWLjwvYXV0aG9yPjxhdXRob3I+TWNIdXRjaGlzb24sIEMuIEEuPC9hdXRob3I+PGF1dGhvcj5D
dm9ybywgVi48L2F1dGhvcj48YXV0aG9yPlNoZW5raW4sIFMuIEQuPC9hdXRob3I+PGF1dGhvcj5X
YXJkbGF3LCBKLiBNLjwvYXV0aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48YXV0aC1hZGRy
ZXNzPkZyb20gdGhlIENlbnRyZSBmb3IgQ2xpbmljYWwgQnJhaW4gU2NpZW5jZXMgKEUuVi5CLiwg
Qy5BLk0uLCBWLkMuLCBKLk0uVy4pLCBDZW50cmUgZm9yIENvZ25pdGl2ZSBBZ2VpbmcgYW5kIENv
Z25pdGl2ZSBFcGlkZW1pb2xvZ3kgKEMuQS5NLiwgVi5DLiwgUy5ELlMuLCBKLk0uVy4pLCBhbmQg
R2VyaWF0cmljIE1lZGljaW5lLCBEZXBhcnRtZW50IG9mIENsaW5pY2FsIGFuZCBTdXJnaWNhbCBT
Y2llbmNlcyAoUy5ELlMuKSwgVW5pdmVyc2l0eSBvZiBFZGluYnVyZ2g7IGFuZCBTY290dGlzaCBJ
bWFnaW5nIE5ldHdvcmsgKFYuQy4sIFMuRC5TLiwgSi5NLlcuKSwgQSBQbGF0Zm9ybSBmb3IgU2Np
ZW50aWZpYyBFeGNlbGxlbmNlIChTSU5BUFNFKSwgVUsuJiN4RDtGcm9tIHRoZSBDZW50cmUgZm9y
IENsaW5pY2FsIEJyYWluIFNjaWVuY2VzIChFLlYuQi4sIEMuQS5NLiwgVi5DLiwgSi5NLlcuKSwg
Q2VudHJlIGZvciBDb2duaXRpdmUgQWdlaW5nIGFuZCBDb2duaXRpdmUgRXBpZGVtaW9sb2d5IChD
LkEuTS4sIFYuQy4sIFMuRC5TLiwgSi5NLlcuKSwgYW5kIEdlcmlhdHJpYyBNZWRpY2luZSwgRGVw
YXJ0bWVudCBvZiBDbGluaWNhbCBhbmQgU3VyZ2ljYWwgU2NpZW5jZXMgKFMuRC5TLiksIFVuaXZl
cnNpdHkgb2YgRWRpbmJ1cmdoOyBhbmQgU2NvdHRpc2ggSW1hZ2luZyBOZXR3b3JrIChWLkMuLCBT
LkQuUy4sIEouTS5XLiksIEEgUGxhdGZvcm0gZm9yIFNjaWVudGlmaWMgRXhjZWxsZW5jZSAoU0lO
QVBTRSksIFVLLiBqb2FubmEud2FyZGxhd0BlZC5hYy51ay48L2F1dGgtYWRkcmVzcz48dGl0bGVz
Pjx0aXRsZT5FYXJseSBsaWZlIHJpc2sgZmFjdG9ycyBmb3IgY2VyZWJyb3Zhc2N1bGFyIGRpc2Vh
c2U6IEEgc3lzdGVtYXRpYyByZXZpZXcgYW5kIG1ldGEtYW5hbHlzaXM8L3RpdGxlPjxzZWNvbmRh
cnktdGl0bGU+TmV1cm9sb2d5PC9zZWNvbmRhcnktdGl0bGU+PGFsdC10aXRsZT5OZXVyb2xvZ3k8
L2FsdC10aXRsZT48L3RpdGxlcz48cGFnZXM+OTc2LTk4NDwvcGFnZXM+PHZvbHVtZT44ODwvdm9s
dW1lPjxudW1iZXI+MTA8L251bWJlcj48a2V5d29yZHM+PGtleXdvcmQ+Q2VyZWJyb3Zhc2N1bGFy
IERpc29yZGVycy9kaWFnbm9zdGljIGltYWdpbmcvKmVwaWRlbWlvbG9neTwva2V5d29yZD48a2V5
d29yZD5DaGlsZDwva2V5d29yZD48a2V5d29yZD5DaGlsZCBBYnVzZS8qcHN5Y2hvbG9neS9zdGF0
aXN0aWNzICZhbXA7IG51bWVyaWNhbCBkYXRhPC9rZXl3b3JkPjxrZXl3b3JkPkRhdGFiYXNlcywg
QmlibGlvZ3JhcGhpYy9zdGF0aXN0aWNzICZhbXA7IG51bWVyaWNhbCBkYXRhPC9rZXl3b3JkPjxr
ZXl3b3JkPkh1bWFuczwva2V5d29yZD48a2V5d29yZD4qTGlmZSBDaGFuZ2UgRXZlbnRzPC9rZXl3
b3JkPjxrZXl3b3JkPk5ldXJvaW1hZ2luZzwva2V5d29yZD48a2V5d29yZD5SaXNrIEZhY3RvcnM8
L2tleXdvcmQ+PGtleXdvcmQ+U29jaW9lY29ub21pYyBGYWN0b3JzPC9rZXl3b3JkPjwva2V5d29y
ZHM+PGRhdGVzPjx5ZWFyPjIwMTc8L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5NYXIgNzwvZGF0ZT48
L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjE1MjYtNjMyWCAoRWxlY3Ryb25pYykmI3hEOzAwMjgt
Mzg3OCAoTGlua2luZyk8L2lzYm4+PGFjY2Vzc2lvbi1udW0+MjgxODgzMDc8L2FjY2Vzc2lvbi1u
dW0+PHVybHM+PHJlbGF0ZWQtdXJscz48dXJsPmh0dHA6Ly93d3cubmNiaS5ubG0ubmloLmdvdi9w
dWJtZWQvMjgxODgzMDc8L3VybD48L3JlbGF0ZWQtdXJscz48L3VybHM+PGVsZWN0cm9uaWMtcmVz
b3VyY2UtbnVtPjEwLjEyMTIvV05MLjAwMDAwMDAwMDAwMDM2ODc8L2VsZWN0cm9uaWMtcmVzb3Vy
Y2UtbnVtPjwvcmVjb3JkPjwvQ2l0ZT48L0VuZE5vdGU+
ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYWNraG91c2U8L0F1dGhvcj48WWVhcj4yMDE3PC9ZZWFy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ADDIN EN.CITE.DATA [13]. DM is considered as one of the key independent risk factors for the development and exacerbation of ischemic reperfusion injury. DM can induce cerebrovascular diseases, which lead to cranial nerve injuries or die PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MaW5jb2ZmPC9BdXRob3I+PFllYXI+MjAxNzwvWWVhcj48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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MaW5jb2ZmPC9BdXRob3I+PFllYXI+MjAxNzwvWWVhcj48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ADDIN EN.CITE.DATA [14-16]. MALAT1 mediates the production of glucose-induced inflammatory cytokines, namely tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), in the endothelial cells which promote DM-associated vascular insult PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5QdXRoYW52ZWV0aWw8L0F1dGhvcj48WWVhcj4yMDE1PC9Z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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5QdXRoYW52ZWV0aWw8L0F1dGhvcj48WWVhcj4yMDE1PC9Z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ADDIN EN.CITE.DATA [17]. MALAT1, MyD88, IRAK1 and TRAF6 were notably up-regulated by DM-ischemic reperfusion models contrasted to the ischemic reperfusion models both in vivo and in vitro. Subsequently, MyD88-dependent signalling provoked cytokine activation and inflammatory reactions for the development of cerebral ischemic reperfusion injury ADDIN EN.CITE <EndNote><Cite><Author>Gao</Author><Year>2009</Year><RecNum>18</RecNum><DisplayText>[18]</DisplayText><record><rec-number>18</rec-number><foreign-keys><key app="EN" db-id="ftefxe9rma55d4ewzvmpseva9s2zwaassrra" timestamp="0">18</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gao, Y.</author><author>Fang, X.</author><author>Tong, Y.</author><author>Liu, Y.</author><author>Zhang, B.</author></authors></contributors><auth-address>Department of Neurobiology, Basic Medical College, China Medical University, Shenyang, China.</auth-address><titles><title>TLR4-mediated MyD88-dependent signaling pathway is activated by cerebral ischemia-reperfusion in cortex in mice</title><secondary-title>Biomed Pharmacother</secondary-title><alt-title>Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie</alt-title></titles><pages>442-50</pages><volume>63</volume><number>6</number><keywords><keyword>Animals</keyword><keyword>Brain Ischemia/genetics/*physiopathology</keyword><keyword>Cerebral Cortex/physiopathology</keyword><keyword>Gene Expression Regulation</keyword><keyword>Interleukin-1beta/metabolism</keyword><keyword>Mice</keyword><keyword>Myeloid Differentiation Factor 88/*genetics</keyword><keyword>NF-kappa B/metabolism</keyword><keyword>RNA, Messenger/metabolism</keyword><keyword>Reperfusion Injury/genetics/*physiopathology</keyword><keyword>Signal Transduction</keyword><keyword>Time Factors</keyword><keyword>Toll-Like Receptor 4/*genetics</keyword><keyword>Tumor Necrosis Factor-alpha/genetics</keyword></keywords><dates><year>2009</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>1950-6007 (Electronic)
0753-3322 (Linking)</isbn><accession-num>18804339</accession-num><urls><related-urls><url>;[18]. MALAT1 up-regulation increased MyD88 adaptor proteins and TRAF6 as well as IRAK1 and again get into a complex, resulting in the activation of NF-κB cascade reaction ADDIN EN.CITE <EndNote><Cite><Author>Nishida</Author><Year>2017</Year><RecNum>19</RecNum><DisplayText>[19]</DisplayText><record><rec-number>19</rec-number><foreign-keys><key app="EN" db-id="ftefxe9rma55d4ewzvmpseva9s2zwaassrra" timestamp="0">19</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Nishida, A.</author><author>Inatomi, O.</author><author>Fujimoto, T.</author><author>Imaeda, H.</author><author>Tani, M.</author><author>Andoh, A.</author></authors></contributors><auth-address>From the Department of Medicine, Shiga University of Medical Science, Otsu, Japan.</auth-address><titles><title>Interleukin-36alpha Induces Inflammatory Mediators From Human Pancreatic Myofibroblasts Via a MyD88 Dependent Pathway</title><secondary-title>Pancreas</secondary-title><alt-title>Pancreas</alt-title></titles><pages>539-548</pages><volume>46</volume><number>4</number><keywords><keyword>Blotting, Western</keyword><keyword>Cells, Cultured</keyword><keyword>Cytokines/genetics/*metabolism</keyword><keyword>Gene Expression</keyword><keyword>Humans</keyword><keyword>Immunohistochemistry</keyword><keyword>Inflammation Mediators/*metabolism</keyword><keyword>Interleukin-1/genetics/*metabolism</keyword><keyword>Myeloid Differentiation Factor 88/genetics/*metabolism</keyword><keyword>Myofibroblasts/*metabolism</keyword><keyword>Pancreas/cytology/metabolism</keyword><keyword>RNA Interference</keyword><keyword>Receptors, Interleukin/genetics/metabolism</keyword><keyword>*Signal Transduction</keyword></keywords><dates><year>2017</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>1536-4828 (Electronic)
0885-3177 (Linking)</isbn><accession-num>28099250</accession-num><urls><related-urls><url>;[19]. On an overall, the pre-cortical infracted tissues from ischemic reperfusion injury model in diabetic rats showed a severe form of neuronal damage by presenting significant neurological deficit scores and increasingly brain oedema. MALAT1 was therefore as a component for DM-associated cerebral ischemic reperfusion injury via positive regulation of MyD88 expression as well as increasing H3 histone acetylation of the MyD88 promoter ADDIN EN.CITE <EndNote><Cite><Author>Wang</Author><Year>2018</Year><RecNum>20</RecNum><DisplayText>[20]</DisplayText><record><rec-number>20</rec-number><foreign-keys><key app="EN" db-id="ftefxe9rma55d4ewzvmpseva9s2zwaassrra" timestamp="0">20</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Wang, L. Q.</author><author>Zhou, H. J.</author></authors></contributors><auth-address>Department of Anesthesiology, The First Affiliated Hospital of Zhejiang University, Hangzhou, 310003, China.
Department of Neurosurgery, The First Affiliated Hospital of Zhejiang University, Hangzhou, 310003, China. 1510027@zju..</auth-address><titles><title>LncRNA MALAT1 promotes high glucose-induced inflammatory response of microglial cells via provoking MyD88/IRAK1/TRAF6 signaling</title><secondary-title>Sci Rep</secondary-title><alt-title>Scientific reports</alt-title></titles><pages>8346</pages><volume>8</volume><number>1</number><dates><year>2018</year><pub-dates><date>May 29</date></pub-dates></dates><isbn>2045-2322 (Electronic)
2045-2322 (Linking)</isbn><accession-num>29844328</accession-num><urls><related-urls><url>;[20]. Therefore, MALAT1 is obviously an essential regulatory factor for ischemic reperfusion injury due to DM. It could be an effective therapeutic target for the management and future prevention of ischemic reperfusion injury-induced by DM. However, more in-depth studies are needed to give more insights on MALAT1 MyD88 promoter acetylation mechanism.Diabetic Retinopathy Diabetic retinopathy (DR) is a devastating ocular impediment and the leading cause of vision loss among working-age adults in developed countries ADDIN EN.CITE <EndNote><Cite><Author>Klein</Author><Year>2007</Year><RecNum>21</RecNum><DisplayText>[21]</DisplayText><record><rec-number>21</rec-number><foreign-keys><key app="EN" db-id="ftefxe9rma55d4ewzvmpseva9s2zwaassrra" timestamp="0">21</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Klein, B. E.</author></authors></contributors><auth-address>Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53726, USA. kleinb@epi.ophth.wisc.edu</auth-address><titles><title>Overview of epidemiologic studies of diabetic retinopathy</title><secondary-title>Ophthalmic Epidemiol</secondary-title><alt-title>Ophthalmic epidemiology</alt-title></titles><pages>179-83</pages><volume>14</volume><number>4</number><keywords><keyword>Blindness/epidemiology</keyword><keyword>Diabetic Retinopathy/*epidemiology</keyword><keyword>Epidemiologic Studies</keyword><keyword>Humans</keyword><keyword>Incidence</keyword><keyword>Prevalence</keyword><keyword>Quality of Life</keyword></keywords><dates><year>2007</year><pub-dates><date>Jul-Aug</date></pub-dates></dates><isbn>0928-6586 (Print)
0928-6586 (Linking)</isbn><accession-num>17896294</accession-num><urls><related-urls><url>;[21]. Worldwide, the prevalence of DR has been predicted to be 35% and the prevalence of vision-impairing is estimated around 10% PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MZWFzaGVyPC9BdXRob3I+PFllYXI+MjAxNjwvWWVhcj48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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MZWFzaGVyPC9BdXRob3I+PFllYXI+MjAxNjwvWWVhcj48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ADDIN EN.CITE.DATA [22, 23]. Various risk factors such as poor glycaemic control, hypertension, hyperlipidaemia, longer diabetes duration and albuminuria are reported to be the origination and development of DR PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5GdTwvQXV0aG9yPjxZZWFyPjIwMTA8L1llYXI+PFJlY051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==
ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5GdTwvQXV0aG9yPjxZZWFyPjIwMTA8L1llYXI+PFJlY051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==
ADDIN EN.CITE.DATA [24, 25]. Biao et al. reported that MALAT1 is considerably up-regulated in the diabetic mice retinas, RF/6A cell model of hyperglycaemia, aqueous humour samples, and fibrovascular membranes (FVMs) of diabetic patients. Thus, they documented that MALAT1 dysregulation might contribute to the occurrence of DR via the in vitro study, experimental animal study and the analysis of clinical samples ADDIN EN.CITE <EndNote><Cite><Author>Yan</Author><Year>2014</Year><RecNum>26</RecNum><DisplayText>[26]</DisplayText><record><rec-number>26</rec-number><foreign-keys><key app="EN" db-id="ftefxe9rma55d4ewzvmpseva9s2zwaassrra" timestamp="0">26</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Yan, B.</author><author>Tao, Z. F.</author><author>Li, X. M.</author><author>Zhang, H.</author><author>Yao, J.</author><author>Jiang, Q.</author></authors></contributors><auth-address>Eye Hospital, Nanjing Medical University, Nanjing, China.</auth-address><titles><title>Aberrant expression of long noncoding RNAs in early diabetic retinopathy</title><secondary-title>Invest Ophthalmol Vis Sci</secondary-title><alt-title>Investigative ophthalmology & visual science</alt-title></titles><pages>941-51</pages><volume>55</volume><number>2</number><keywords><keyword>Animals</keyword><keyword>Blood Glucose/metabolism</keyword><keyword>Diabetes Mellitus, Experimental/*genetics</keyword><keyword>Diabetic Retinopathy/*genetics</keyword><keyword>Female</keyword><keyword>Gene Expression Profiling</keyword><keyword>Gene Expression Regulation/*physiology</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Mice, Inbred C57BL</keyword><keyword>Oligonucleotide Array Sequence Analysis</keyword><keyword>RNA, Long Noncoding/*genetics</keyword><keyword>RNA, Messenger/genetics</keyword><keyword>Real-Time Polymerase Chain Reaction</keyword><keyword>Retina/metabolism</keyword></keywords><dates><year>2014</year><pub-dates><date>Feb 18</date></pub-dates></dates><isbn>1552-5783 (Electronic)
0146-0404 (Linking)</isbn><accession-num>24436191</accession-num><urls><related-urls><url>;[26]. MALAT1 is also capable of implicating the expressions of inflammatory transcripts through association with the components of the PRC2 complex in diabetes. Likewise, vitreous humour collected from diabetic patients has shown expressions of MALAT1, IL-6, and TNF-α. Unusually, the DNA methylation array revealed that transient high glucose contact in human retinal microvascular endothelium cells (HRECs) does not add to significant methylation modifications at CpG sites through the MALAT1 gene. Conversely, overall inhibition of DNA methyltransferases prompted the major increase in MALAT1 and related inflammatory transcripts in HRECs ADDIN EN.CITE <EndNote><Cite><Author>Biswas</Author><Year>2018</Year><RecNum>27</RecNum><DisplayText>[27]</DisplayText><record><rec-number>27</rec-number><foreign-keys><key app="EN" db-id="ftefxe9rma55d4ewzvmpseva9s2zwaassrra" timestamp="0">27</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Biswas, S.</author><author>Thomas, A. A.</author><author>Chen, S.</author><author>Aref-Eshghi, E.</author><author>Feng, B.</author><author>Gonder, J.</author><author>Sadikovic, B.</author><author>Chakrabarti, S.</author></authors></contributors><auth-address>Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada.
Department of Ophthalmology, Western University, London, Ontario, Canada.
Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada. subrata.chakrabarti@lhsc.on.ca.</auth-address><titles><title>MALAT1: An Epigenetic Regulator of Inflammation in Diabetic Retinopathy</title><secondary-title>Sci Rep</secondary-title><alt-title>Scientific reports</alt-title></titles><pages>6526</pages><volume>8</volume><number>1</number><dates><year>2018</year><pub-dates><date>Apr 25</date></pub-dates></dates><isbn>2045-2322 (Electronic)
2045-2322 (Linking)</isbn><accession-num>29695738</accession-num><urls><related-urls><url>;[27]. Guo et al. also explained that methyl donor could diminish MALAT1 expression in this cells-entailing that DNA methylation involved the regulation of MALAT1 expression PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HdW88L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFyPjxSZWNO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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HdW88L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFyPjxSZWNO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ADDIN EN.CITE.DATA [28]. As a result, it is not a confounding that MALAT1 dysregulation may perhaps disrupt the proliferation and migration of FVM-related cells, which affect the DR pathogenesis. In another study, MALAT 1 expression was highly up-regulated in STZ-induced diabetic rat’s retina and db/db mice. MALAT1 ablation enhances DR in vivo. Furthermore, MALAT1 knockdown regulates migration and retinal endothelial cell proliferation. MALAT1 over-expression denotes a crucial pathogenic mechanism for diabetes-related microvascular dysfunction, hyperproliferation of endothelial cells through p38MAPK signalling. MALAT1 inhibition may become a potent anti-angiogenic therapy for diabetic microvascular complications PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MaXU8L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFyPjxSZWNO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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MaXU8L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFyPjxSZWNO
dW0+Mjk8L1JlY051bT48RGlzcGxheVRleHQ+WzI5XTwvRGlzcGxheVRleHQ+PHJlY29yZD48cmVj
LW51bWJlcj4yOTwvcmVjLW51bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9
ImZ0ZWZ4ZTlybWE1NWQ0ZXd6dm1wc2V2YTlzMnp3YWFzc3JyYSIgdGltZXN0YW1wPSIwIj4yOTwv
a2V5PjwvZm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJKb3VybmFsIEFydGljbGUiPjE3PC9y
ZWYtdHlwZT48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+TGl1LCBKLiBZLjwvYXV0aG9y
PjxhdXRob3I+WWFvLCBKLjwvYXV0aG9yPjxhdXRob3I+TGksIFguIE0uPC9hdXRob3I+PGF1dGhv
cj5Tb25nLCBZLiBDLjwvYXV0aG9yPjxhdXRob3I+V2FuZywgWC4gUS48L2F1dGhvcj48YXV0aG9y
PkxpLCBZLiBKLjwvYXV0aG9yPjxhdXRob3I+WWFuLCBCLjwvYXV0aG9yPjxhdXRob3I+Smlhbmcs
IFEuPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjxhdXRoLWFkZHJlc3M+MV0gRXll
IEhvc3BpdGFsLCBOYW5qaW5nIE1lZGljYWwgVW5pdmVyc2l0eSwgTmFuamluZywgQ2hpbmEgWzJd
IFRoZSBGb3VydGggU2Nob29sIG9mIENsaW5pY2FsIE1lZGljaW5lLCBOYW5qaW5nIE1lZGljYWwg
VW5pdmVyc2l0eSwgTmFuamluZywgQ2hpbmEuJiN4RDtFeWUgSG9zcGl0YWwsIE5hbmppbmcgTWVk
aWNhbCBVbml2ZXJzaXR5LCBOYW5qaW5nLCBDaGluYS4mI3hEOzFdIEV5ZSBIb3NwaXRhbCwgTmFu
amluZyBNZWRpY2FsIFVuaXZlcnNpdHksIE5hbmppbmcsIENoaW5hIFsyXSBUaGUgRm91cnRoIFNj
aG9vbCBvZiBDbGluaWNhbCBNZWRpY2luZSwgTmFuamluZyBNZWRpY2FsIFVuaXZlcnNpdHksIE5h
bmppbmcsIENoaW5hIFszXSBJbnN0aXR1dGUgb2YgSW50ZWdyYXRlZCBNZWRpY2luZSwgTmFuamlu
ZyBNZWRpY2FsIFVuaXZlcnNpdHksIE5hbmppbmcsIENoaW5hLjwvYXV0aC1hZGRyZXNzPjx0aXRs
ZXM+PHRpdGxlPlBhdGhvZ2VuaWMgcm9sZSBvZiBsbmNSTkEtTUFMQVQxIGluIGVuZG90aGVsaWFs
IGNlbGwgZHlzZnVuY3Rpb24gaW4gZGlhYmV0ZXMgbWVsbGl0dXM8L3RpdGxlPjxzZWNvbmRhcnkt
dGl0bGU+Q2VsbCBEZWF0aCBEaXM8L3NlY29uZGFyeS10aXRsZT48YWx0LXRpdGxlPkNlbGwgZGVh
dGggJmFtcDsgZGlzZWFzZTwvYWx0LXRpdGxlPjwvdGl0bGVzPjxwYWdlcz5lMTUwNjwvcGFnZXM+
PHZvbHVtZT41PC92b2x1bWU+PGtleXdvcmRzPjxrZXl3b3JkPkFuaW1hbHM8L2tleXdvcmQ+PGtl
eXdvcmQ+Q2VsbCBNb3ZlbWVudDwva2V5d29yZD48a2V5d29yZD5DZWxsIFByb2xpZmVyYXRpb248
L2tleXdvcmQ+PGtleXdvcmQ+Q2VsbCBTdXJ2aXZhbDwva2V5d29yZD48a2V5d29yZD5EaWFiZXRl
cyBNZWxsaXR1cywgRXhwZXJpbWVudGFsLypnZW5ldGljcy9wYXRob2xvZ3kvKnBoeXNpb3BhdGhv
bG9neTwva2V5d29yZD48a2V5d29yZD5EaXNlYXNlIE1vZGVscywgQW5pbWFsPC9rZXl3b3JkPjxr
ZXl3b3JkPkVuZG90aGVsaWFsIENlbGxzL21ldGFib2xpc20vKnBhdGhvbG9neTwva2V5d29yZD48
a2V5d29yZD5HZW5lIEtub2NrZG93biBUZWNobmlxdWVzPC9rZXl3b3JkPjxrZXl3b3JkPkluZmxh
bW1hdGlvbjwva2V5d29yZD48a2V5d29yZD5NQVAgS2luYXNlIFNpZ25hbGluZyBTeXN0ZW08L2tl
eXdvcmQ+PGtleXdvcmQ+TWljZTwva2V5d29yZD48a2V5d29yZD5OZW92YXNjdWxhcml6YXRpb24s
IFBoeXNpb2xvZ2ljPC9rZXl3b3JkPjxrZXl3b3JkPlJOQSwgTG9uZyBOb25jb2RpbmcvKm1ldGFi
b2xpc208L2tleXdvcmQ+PGtleXdvcmQ+UmF0czwva2V5d29yZD48a2V5d29yZD5SZXRpbmFsIFZl
c3NlbHMvcGF0aG9sb2d5L3BoeXNpb3BhdGhvbG9neTwva2V5d29yZD48a2V5d29yZD5VcC1SZWd1
bGF0aW9uL2dlbmV0aWNzPC9rZXl3b3JkPjxrZXl3b3JkPnAzOCBNaXRvZ2VuLUFjdGl2YXRlZCBQ
cm90ZWluIEtpbmFzZXMvbWV0YWJvbGlzbTwva2V5d29yZD48L2tleXdvcmRzPjxkYXRlcz48eWVh
cj4yMDE0PC95ZWFyPjxwdWItZGF0ZXM+PGRhdGU+T2N0IDMwPC9kYXRlPjwvcHViLWRhdGVzPjwv
ZGF0ZXM+PGlzYm4+MjA0MS00ODg5IChFbGVjdHJvbmljKTwvaXNibj48YWNjZXNzaW9uLW51bT4y
NTM1Njg3NTwvYWNjZXNzaW9uLW51bT48dXJscz48cmVsYXRlZC11cmxzPjx1cmw+aHR0cDovL3d3
dy5uY2JpLm5sbS5uaWguZ292L3B1Ym1lZC8yNTM1Njg3NTwvdXJsPjwvcmVsYXRlZC11cmxzPjwv
dXJscz48Y3VzdG9tMj40NjQ5NTM5PC9jdXN0b20yPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4x
MC4xMDM4L2NkZGlzLjIwMTQuNDY2PC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48L3JlY29yZD48
L0NpdGU+PC9FbmROb3RlPn==
ADDIN EN.CITE.DATA [29]. All these findings collectively determine the impact of MALAT1 in inflammation and epigenetic regulation in DR. In conclusion, MALAT1 a preserved lncRNA may turn out to be a potential biomarker for the diagnosis and prognosis of DR. More studies are essential to examine the correlations among lncRNA change and DR development at different stages. Additionally, in vivo and in vitro studies should be conducted to clarify the molecular mechanisms of lncRNA mediated DR occurrence and evaluate their potential for the diagnosis, prognosis and treatment of DR.Diabetic Cataract Diabetic cataract (DC) commonly occurs earlier and develops rapidly PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IYXJkaW5nPC9BdXRob3I+PFllYXI+MTk5MzwvWWVhcj48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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IYXJkaW5nPC9BdXRob3I+PFllYXI+MTk5MzwvWWVhcj48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ADDIN EN.CITE.DATA [30, 31]. Regardless of the successful implantation with synthetic intraocular lenses, cataract remains one of the leading causes of blindness PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Qb2xscmVpc3o8L0F1dGhvcj48WWVhcj4yMDEwPC9ZZWFy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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Qb2xscmVpc3o8L0F1dGhvcj48WWVhcj4yMDEwPC9ZZWFy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ADDIN EN.CITE.DATA [32, 33]. Although there are no treatment guidelines for DC, there is a need to understand the progression and pathogenesis of cataract formation to deliver therapeutic targets for the prevention and treatment of DC apart from surgical methods. A recent study revealed that the expression of MALAT1 was elevated in diabetic cataract tissues cells, hyperglycaemia (HG)-induced human lens epithelial cells (HLECs) as well as up-regulated by HG to provoke the apoptosis and oxidative stress of HLECs. Moreover, HG prompted the up-regulation of MALAT1 by SP1 binding of MALAT1 promoter regions to exert its role in the apoptosis oxidative stress of HLECs ADDIN EN.CITE <EndNote><Cite><Author>Lei</Author><Year>2018</Year><RecNum>12</RecNum><DisplayText>[12]</DisplayText><record><rec-number>12</rec-number><foreign-keys><key app="EN" db-id="ftefxe9rma55d4ewzvmpseva9s2zwaassrra" timestamp="0">12</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lei, L.</author><author>Chen, J.</author><author>Huang, J.</author><author>Lu, J.</author><author>Pei, S.</author><author>Ding, S.</author><author>Kang, L.</author><author>Xiao, R.</author><author>Zeng, Q.</author></authors></contributors><auth-address>Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Department of Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Department of Dermatology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Department of Dermatology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.</auth-address><titles><title>Functions and regulatory mechanisms of metastasis-associated lung adenocarcinoma transcript 1</title><secondary-title>J Cell Physiol</secondary-title><alt-title>Journal of cellular physiology</alt-title></titles><dates><year>2018</year><pub-dates><date>Aug 21</date></pub-dates></dates><isbn>1097-4652 (Electronic)
0021-9541 (Linking)</isbn><accession-num>30132842</accession-num><urls><related-urls><url>;[12]. Yuan et al. further studied the mechanism between MALAT1 and the apoptosis as well as oxidative stress of HLECs and discovered that p38MAPK was up-regulated in HG-treated HLECs. Likewise, previous studies demonstrated that p38MAPK play a pivotal role in HLEC activity and apoptosis induced by oxidative stress PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5ZdWFuPC9BdXRob3I+PFllYXI+MjAxMzwvWWVhcj48UmVj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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5ZdWFuPC9BdXRob3I+PFllYXI+MjAxMzwvWWVhcj48UmVj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ADDIN EN.CITE.DATA [34-36]. Meanwhile, knockdown of p38MAPK restrained the influence of MALAT1 over-expression on HLECs [37]. Hence, it was confirmed that MALAT1 promote the apoptosis and oxidative stress of HLECs through the initiation of the p38MAPK signalling pathway ADDIN EN.CITE <EndNote><Cite><Author>Gong</Author><Year>2018</Year><RecNum>42</RecNum><DisplayText>[37]</DisplayText><record><rec-number>42</rec-number><foreign-keys><key app="EN" db-id="ftefxe9rma55d4ewzvmpseva9s2zwaassrra" timestamp="0">42</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gong, W.</author><author>Zhu, G.</author><author>Li, J.</author><author>Yang, X.</author></authors></contributors><auth-address>Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Department of Ophthalmology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Department of Ophthalmology, The Henan Provincial People's Hospital, Zhengzhou, Henan, China.
Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. Electronic address: Xin_Yang123@.</auth-address><titles><title>TEMPORARY REMOVAL: "LncRNA MALAT1 promotes the apoptosis and oxidative stress of human lens epithelial cells via p38MAPK pathway in diabetic cataract"</title><secondary-title>Diabetes Res Clin Pract</secondary-title><alt-title>Diabetes research and clinical practice</alt-title></titles><dates><year>2018</year><pub-dates><date>Jun 22</date></pub-dates></dates><isbn>1872-8227 (Electronic)
0168-8227 (Linking)</isbn><accession-num>29936249</accession-num><urls><related-urls><url>;[37]. Thus, MALAT1 might be a likely therapeutic target for DC.AtherosclerosisHyperglycemia is recognized as an independent cardiovascular risk factor. It can accelerate and heightened atherosclerosis, which is a principal reason for morbidity as well as mortality in DM PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TaHJpa2hhbmRlPC9BdXRob3I+PFllYXI+MjAxMDwvWWVh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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TaHJpa2hhbmRlPC9BdXRob3I+PFllYXI+MjAxMDwvWWVh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ADDIN EN.CITE.DATA [38]. The incidence of coronary heart disease and peripheral vascular disease?increases to 4 times and more 10 times in a patient with DM as compared to the normal individual PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5GYXhvbjwvQXV0aG9yPjxZZWFyPjIwMDQ8L1llYXI+PFJl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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5GYXhvbjwvQXV0aG9yPjxZZWFyPjIwMDQ8L1llYXI+PFJl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ADDIN EN.CITE.DATA [39]. Therefore, it begs to discover the precise molecular processes involved in the development as well as acceleration of atherosclerosis in DM patient and to accomplish possible therapeutic targets. Recent evidence revealed that inflammation coupled with over-activated innate immunity is strongly associated with the pathogenesis of DM and related complications comprising atherosclerosis ADDIN EN.CITE <EndNote><Cite><Author>Dandona</Author><Year>2004</Year><RecNum>45</RecNum><DisplayText>[40]</DisplayText><record><rec-number>45</rec-number><foreign-keys><key app="EN" db-id="ftefxe9rma55d4ewzvmpseva9s2zwaassrra" timestamp="0">45</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Dandona, P.</author><author>Aljada, A.</author><author>Bandyopadhyay, A.</author></authors></contributors><auth-address>Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo and Kaleida Health, 3 Gates Circle, Buffalo, NY 14209, USA. pdondona@</auth-address><titles><title>Inflammation: the link between insulin resistance, obesity and diabetes</title><secondary-title>Trends Immunol</secondary-title><alt-title>Trends in immunology</alt-title></titles><pages>4-7</pages><volume>25</volume><number>1</number><keywords><keyword>Animals</keyword><keyword>Diabetes Mellitus, Type 2/etiology/*physiopathology</keyword><keyword>Diet</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Inflammation/complications/*physiopathology</keyword><keyword>Insulin/pharmacology</keyword><keyword>Insulin Resistance/*physiology</keyword><keyword>Male</keyword><keyword>Obesity/complications/*physiopathology</keyword><keyword>Oxidative Stress/drug effects</keyword><keyword>Risk Factors</keyword></keywords><dates><year>2004</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>1471-4906 (Print)
1471-4906 (Linking)</isbn><accession-num>14698276</accession-num><urls><related-urls><url>;[40]. It was revealed that MALAT1 plays an important role in the development and acceleration of diabetic atherosclerosis. Han et al. found that MALAT1 was highly expressed in the macrophages of diabetic atherosclerosis rats along with hypernomic stimulation of NLRP3 inflammasome though sponging miR-23c as well as an increase in the building of systemic inflammatory cytokines. They also suggested that the administration of low-dose sinapic acid (SA) suppresses MALAT1-mediated NLRP3 inflammasome activation, pyroptosis of macrophages as well as generalized inflammation ADDIN EN.CITE <EndNote><Cite><Author>Han</Author><Year>2018</Year><RecNum>46</RecNum><DisplayText>[41]</DisplayText><record><rec-number>46</rec-number><foreign-keys><key app="EN" db-id="ftefxe9rma55d4ewzvmpseva9s2zwaassrra" timestamp="0">46</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Han, Y.</author><author>Qiu, H.</author><author>Pei, X.</author><author>Fan, Y.</author><author>Tian, H.</author><author>Geng, J.</author></authors></contributors><auth-address>Internal Medicine, Hong-Hui Hospital, Xi'an Jiaotong University College of Medicine, Xi'an, China.
Peripheral Vascular Section, Xi'an Jiaotong University College of Medicine, Xi'an, China.</auth-address><titles><title>Low-dose Sinapic Acid Abates the Pyroptosis of Macrophages by Downregulation of lncRNA-MALAT1 in Rats With Diabetic Atherosclerosis</title><secondary-title>J Cardiovasc Pharmacol</secondary-title><alt-title>Journal of cardiovascular pharmacology</alt-title></titles><pages>104-112</pages><volume>71</volume><number>2</number><dates><year>2018</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>1533-4023 (Electronic)
0160-2446 (Linking)</isbn><accession-num>29095793</accession-num><urls><related-urls><url>;[41]. To sum up, MALAT1 might act as an inflammatory factor in the development of diabetic atherosclerosis. The interaction between MALAT1 and low-dose SA may provide a new therapeutic direction in diabetic atherosclerosis.Diabetic Cardiomyopathy Diabetic cardiomyopathy (DC) is an essential cardiovascular system (CVS) complication of DM characterized by a variability of morphological changes, comprising myocyte hypertrophy, myofibril depletion, interstitial fibrosis, as well as intramyocardial microangiopathy ADDIN EN.CITE <EndNote><Cite><Author>Falcao-Pires</Author><Year>2012</Year><RecNum>47</RecNum><DisplayText>[42]</DisplayText><record><rec-number>47</rec-number><foreign-keys><key app="EN" db-id="ftefxe9rma55d4ewzvmpseva9s2zwaassrra" timestamp="0">47</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Falcao-Pires, I.</author><author>Leite-Moreira, A. F.</author></authors></contributors><auth-address>Department of Physiology and Cardiothoracic Surgery, Cardiovascular R&D Unit, University of Porto, Porto, Portugal.</auth-address><titles><title>Diabetic cardiomyopathy: understanding the molecular and cellular basis to progress in diagnosis and treatment</title><secondary-title>Heart Fail Rev</secondary-title><alt-title>Heart failure reviews</alt-title></titles><pages>325-44</pages><volume>17</volume><number>3</number><keywords><keyword>Diabetic Cardiomyopathies/complications/metabolism/*physiopathology</keyword><keyword>Humans</keyword><keyword>Hyperglycemia/*complications/metabolism/therapy</keyword><keyword>Insulin Resistance/*physiology</keyword><keyword>Myocytes, Cardiac/*metabolism/pathology</keyword><keyword>Oxidative Stress/physiology</keyword><keyword>Ventricular Dysfunction</keyword></keywords><dates><year>2012</year><pub-dates><date>May</date></pub-dates></dates><isbn>1573-7322 (Electronic)
1382-4147 (Linking)</isbn><accession-num>21626163</accession-num><urls><related-urls><url>;[42]. It arises autonomously from hypertension, dyslipidemia as well as coronary artery disease and bears a considerable risk for the sequential development of clinical heart failure along with higher morbidity as well as mortality PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5KaWE8L0F1dGhvcj48WWVhcj4yMDE4PC9ZZWFyPjxSZWNO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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5KaWE8L0F1dGhvcj48WWVhcj4yMDE4PC9ZZWFyPjxSZWNO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ADDIN EN.CITE.DATA [43]. High blood sugar level is a main etiological factor responsible in the occurrence of DC and upsurges the risk of heart failure by numerous folds PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TdTwvQXV0aG9yPjxZZWFyPjIwMTc8L1llYXI+PFJlY051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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TdTwvQXV0aG9yPjxZZWFyPjIwMTc8L1llYXI+PFJlY051
bT40OTwvUmVjTnVtPjxEaXNwbGF5VGV4dD5bNDRdPC9EaXNwbGF5VGV4dD48cmVjb3JkPjxyZWMt
bnVtYmVyPjQ5PC9yZWMtbnVtYmVyPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0i
ZnRlZnhlOXJtYTU1ZDRld3p2bXBzZXZhOXMyendhYXNzcnJhIiB0aW1lc3RhbXA9IjAiPjQ5PC9r
ZXk+PC9mb3JlaWduLWtleXM+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3Jl
Zi10eXBlPjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5TdSwgWC4gRi48L2F1dGhvcj48
YXV0aG9yPlN1biwgTC48L2F1dGhvcj48YXV0aG9yPkxpdSwgQi4gTC48L2F1dGhvcj48YXV0aG9y
PlRhbywgWC4gSi48L2F1dGhvcj48YXV0aG9yPkxpLCBILiBRLjwvYXV0aG9yPjxhdXRob3I+TGks
IEYuIEYuPC9hdXRob3I+PGF1dGhvcj5ZZSwgTC48L2F1dGhvcj48YXV0aG9yPkxlZSwgSy4gTy48
L2F1dGhvcj48YXV0aG9yPk1hLCBKLiBILjwvYXV0aG9yPjxhdXRob3I+Q2hlbiwgUy4gTC48L2F1
dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgtYWRkcmVzcz5EZXBhcnRtZW50IG9m
IEVuZG9jcmlub2xvZ3ksIE5hbmppbmcgRmlyc3QgSG9zcGl0YWwsIE5hbmppbmcgTWVkaWNhbCBV
bml2ZXJzaXR5LCBOYW5qaW5nLCBDaGluYS4mI3hEO05hdGlvbmFsIEhlYXJ0IFJlc2VhcmNoIElu
c3RpdHV0ZSBTaW5nYXBvcmUsIE5hdGlvbmFsIEhlYXJ0IENlbnRyZSBTaW5nYXBvcmUsIFNpbmdh
cG9yZS4mI3hEO0RlcGFydG1lbnQgb2YgTWVkaWNpbmUsIE5hdGlvbmFsIFVuaXZlcnNpdHkgb2Yg
U2luZ2Fwb3JlLCBTaW5nYXBvcmUuJiN4RDtEZXBhcnRtZW50IG9mIENhcmRpb2xvZ3ksIE5hbmpp
bmcgRmlyc3QgSG9zcGl0YWwsIE5hbmppbmcgTWVkaWNhbCBVbml2ZXJzaXR5LCBOYW5qaW5nLCBD
aGluYS48L2F1dGgtYWRkcmVzcz48dGl0bGVzPjx0aXRsZT5BbiBJbnRlbnNpdmUgRGlhYmV0ZXMg
U2NyZWVuaW5nIGFuZCBUcmVhdG1lbnQgUHJvZ3JhbSBJbXByb3ZlcyBEaWFnbm9zaXMsIFRyZWF0
bWVudCBhbmQgT3V0Y29tZXMgb2YgRGlhYmV0ZXMgaW4gUGF0aWVudHMgQWRtaXR0ZWQgd2l0aCBD
YXJkaWFjIERpc2Vhc2VzPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkV4cCBDbGluIEVuZG9jcmlu
b2wgRGlhYmV0ZXM8L3NlY29uZGFyeS10aXRsZT48YWx0LXRpdGxlPkV4cGVyaW1lbnRhbCBhbmQg
Y2xpbmljYWwgZW5kb2NyaW5vbG9neSAmYW1wOyBkaWFiZXRlcyA6IG9mZmljaWFsIGpvdXJuYWws
IEdlcm1hbiBTb2NpZXR5IG9mIEVuZG9jcmlub2xvZ3kgW2FuZF0gR2VybWFuIERpYWJldGVzIEFz
c29jaWF0aW9uPC9hbHQtdGl0bGU+PC90aXRsZXM+PHBhZ2VzPjE1MS0xNTU8L3BhZ2VzPjx2b2x1
bWU+MTI1PC92b2x1bWU+PG51bWJlcj4zPC9udW1iZXI+PGtleXdvcmRzPjxrZXl3b3JkPkFkdWx0
PC9rZXl3b3JkPjxrZXl3b3JkPkNoaW5hPC9rZXl3b3JkPjxrZXl3b3JkPkNvc3RzIGFuZCBDb3N0
IEFuYWx5c2lzPC9rZXl3b3JkPjxrZXl3b3JkPipEaWFiZXRlcyBNZWxsaXR1cy9kaWFnbm9zaXMv
ZWNvbm9taWNzL3N1cmdlcnk8L2tleXdvcmQ+PGtleXdvcmQ+RmVtYWxlPC9rZXl3b3JkPjxrZXl3
b3JkPipIZWFydCBEaXNlYXNlcy9kaWFnbm9zaXMvZWNvbm9taWNzL3N1cmdlcnk8L2tleXdvcmQ+
PGtleXdvcmQ+SHVtYW5zPC9rZXl3b3JkPjxrZXl3b3JkPk1hbGU8L2tleXdvcmQ+PGtleXdvcmQ+
TWFzcyBTY3JlZW5pbmc8L2tleXdvcmQ+PGtleXdvcmQ+UGVyY3V0YW5lb3VzIENvcm9uYXJ5IElu
dGVydmVudGlvbi8qZWNvbm9taWNzPC9rZXl3b3JkPjwva2V5d29yZHM+PGRhdGVzPjx5ZWFyPjIw
MTc8L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5NYXI8L2RhdGU+PC9wdWItZGF0ZXM+PC9kYXRlcz48
aXNibj4xNDM5LTM2NDYgKEVsZWN0cm9uaWMpJiN4RDswOTQ3LTczNDkgKExpbmtpbmcpPC9pc2Ju
PjxhY2Nlc3Npb24tbnVtPjI3NzUwMzUzPC9hY2Nlc3Npb24tbnVtPjx1cmxzPjxyZWxhdGVkLXVy
bHM+PHVybD5odHRwOi8vd3d3Lm5jYmkubmxtLm5paC5nb3YvcHVibWVkLzI3NzUwMzUzPC91cmw+
PC9yZWxhdGVkLXVybHM+PC91cmxzPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4xMC4xMDU1L3Mt
MDA0Mi0xMTYzMTI8L2VsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjwvcmVjb3JkPjwvQ2l0ZT48L0Vu
ZE5vdGU+AG==
ADDIN EN.CITE.DATA [44]. CVS diseases are responsible for the utmost mortality rate. Hence, it is evident that initial prevention, as well as the development of cardiac function, would significantly decrease the prevalence. Zhang et al. suggested that MALAT1 was considerably upregulated in DM rats. In addition, TNF-α, IL-1β along with IL-6 levels were uncharacteristically high in the diabetic myocardium. MALAT1 knockdown could appreciably decrease inflammatory cytokine concentration, signifying that MALAT1 might be involved in the development of DCM PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5aaGFuZzwvQXV0aG9yPjxZZWFyPjIwMTY8L1llYXI+PFJl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 EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5aaGFuZzwvQXV0aG9yPjxZZWFyPjIwMTY8L1llYXI+PFJl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 EN.CITE.DATA [45]. Furthermore, MALAT1 knockdown could significantly decrease cardiomyocyte apoptosis in the DM positive MALAT1-shRNA group ADDIN EN.CITE <EndNote><Cite><Author>Zhang</Author><Year>2016</Year><RecNum>51</RecNum><DisplayText>[46]</DisplayText><record><rec-number>51</rec-number><foreign-keys><key app="EN" db-id="ftefxe9rma55d4ewzvmpseva9s2zwaassrra" timestamp="0">51</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Zhang, M.</author><author>Gu, H.</author><author>Xu, W.</author><author>Zhou, X.</author></authors></contributors><auth-address>Department of Cardiology, The First People's Hospital of Kunshan Affiliated to Jiangsu University, Kunshan, China.
Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou, China. Electronic address: zhou-xiang@suda..</auth-address><titles><title>Down-regulation of lncRNA MALAT1 reduces cardiomyocyte apoptosis and improves left ventricular function in diabetic rats</title><secondary-title>Int J Cardiol</secondary-title><alt-title>International journal of cardiology</alt-title></titles><pages>214-6</pages><volume>203</volume><keywords><keyword>Animals</keyword><keyword>*Apoptosis/drug effects</keyword><keyword>Diabetes Mellitus, Experimental/complications/physiopathology</keyword><keyword>*Down-Regulation</keyword><keyword>Male</keyword><keyword>Myocytes, Cardiac/*pathology</keyword><keyword>RNA, Long Noncoding/pharmacology/*physiology/therapeutic use</keyword><keyword>Rats</keyword><keyword>Rats, Sprague-Dawley</keyword><keyword>Ventricular Dysfunction, Left/*drug therapy/etiology</keyword><keyword>*Ventricular Function, Left/drug effects</keyword></keywords><dates><year>2016</year><pub-dates><date>Jan 15</date></pub-dates></dates><isbn>1874-1754 (Electronic)
0167-5273 (Linking)</isbn><accession-num>26512840</accession-num><urls><related-urls><url>;[46]. In another study, Bacci et al. concluded that decrease of nitric oxide (NO) or cGMP bio-availability produced by long-standing DM impairs lncRNA expression as well as sildenafil and reestablishing function of NO signaling normalized MALAT1 expression levels, reducing the cardiac symptoms ADDIN EN.CITE <EndNote><Cite><Author>Bacci</Author><Year>2018</Year><RecNum>52</RecNum><DisplayText>[47]</DisplayText><record><rec-number>52</rec-number><foreign-keys><key app="EN" db-id="ftefxe9rma55d4ewzvmpseva9s2zwaassrra" timestamp="0">52</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Bacci, L.</author><author>Barbati, S. A.</author><author>Colussi, C.</author><author>Aiello, A.</author><author>Isidori, A. M.</author><author>Grassi, C.</author><author>Pontecorvi, A.</author><author>Farsetti, A.</author><author>Gaetano, C.</author><author>Nanni, S.</author></authors></contributors><auth-address>Institute of Medical Pathology, Universita Cattolica di Roma, 00168, Rome, Italy.
Institute of Human Physiology, Universita Cattolica di Roma, 00168, Rome, Italy.
Institute of Cell Biology and Neurobiology, National Research Council, 00143, Rome, Italy.
Department of Experimental Medicine, "Sapienza" University, 00161, Rome, Italy.
Fondazione Policlinico Universitario Gemelli, 00168, Rome, Italy.
Laboratorio di Epigenetica, Istituti Clinici Scientifici Maugeri, via Maugeri 4, 27100, Pavia, Italy. carlo.gaetano@icsmaugeri.it.
Institute of Medical Pathology, Universita Cattolica di Roma, 00168, Rome, Italy. simona.nanni@unicatt.it.</auth-address><titles><title>Sildenafil normalizes MALAT1 level in diabetic cardiomyopathy</title><secondary-title>Endocrine</secondary-title><alt-title>Endocrine</alt-title></titles><dates><year>2018</year><pub-dates><date>Apr 24</date></pub-dates></dates><isbn>1559-0100 (Electronic)
1355-008X (Linking)</isbn><accession-num>29691810</accession-num><urls><related-urls><url>;[47]. In conclusion, MALAT1 is considerably overexpressed in cardiac tissue of DM rats, and its inhibition results in improvement in the cardiac function. Thus, knockdown of MALAT1 may serve as a novel therapeutic approach for DC. Non-alcoholic SteatohepatitisNon-alcoholic steatohepatitis (NASH) is recognized as the major cause of chronic liver disease as well as an important cause of cryptogenic cirrhosis ADDIN EN.CITE <EndNote><Cite><Author>Starley</Author><Year>2010</Year><RecNum>53</RecNum><DisplayText>[48]</DisplayText><record><rec-number>53</rec-number><foreign-keys><key app="EN" db-id="ftefxe9rma55d4ewzvmpseva9s2zwaassrra" timestamp="0">53</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Starley, B. Q.</author><author>Calcagno, C. J.</author><author>Harrison, S. A.</author></authors></contributors><auth-address>Department of Medicine, Division of Gastroenterology and Hepatology, Brooke Army Medical Center, Fort Sam Houston, TX 78234, USA.</auth-address><titles><title>Nonalcoholic fatty liver disease and hepatocellular carcinoma: a weighty connection</title><secondary-title>Hepatology</secondary-title><alt-title>Hepatology</alt-title></titles><pages>1820-32</pages><volume>51</volume><number>5</number><keywords><keyword>Age Factors</keyword><keyword>Carcinoma, Hepatocellular/*etiology</keyword><keyword>*Diabetes Complications</keyword><keyword>Fatty Liver/*complications</keyword><keyword>Hepatitis C, Chronic/complications</keyword><keyword>Humans</keyword><keyword>Iron/metabolism</keyword><keyword>Liver/metabolism</keyword><keyword>Liver Cirrhosis/etiology</keyword><keyword>Liver Neoplasms/*etiology</keyword><keyword>Obesity/*complications</keyword><keyword>Risk Factors</keyword></keywords><dates><year>2010</year><pub-dates><date>May</date></pub-dates></dates><isbn>1527-3350 (Electronic)
0270-9139 (Linking)</isbn><accession-num>20432259</accession-num><urls><related-urls><url>;[48]. NASH patients experience higher liver associated morbidity along with mortality PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NYXR0ZW9uaTwvQXV0aG9yPjxZZWFyPjE5OTk8L1llYXI+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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NYXR0ZW9uaTwvQXV0aG9yPjxZZWFyPjE5OTk8L1llYXI+
PFJlY051bT41NDwvUmVjTnVtPjxEaXNwbGF5VGV4dD5bNDksIDUwXTwvRGlzcGxheVRleHQ+PHJl
Y29yZD48cmVjLW51bWJlcj41NDwvcmVjLW51bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJF
TiIgZGItaWQ9ImZ0ZWZ4ZTlybWE1NWQ0ZXd6dm1wc2V2YTlzMnp3YWFzc3JyYSIgdGltZXN0YW1w
PSIwIj41NDwva2V5PjwvZm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJKb3VybmFsIEFydGlj
bGUiPjE3PC9yZWYtdHlwZT48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+TWF0dGVvbmks
IEMuIEEuPC9hdXRob3I+PGF1dGhvcj5Zb3Vub3NzaSwgWi4gTS48L2F1dGhvcj48YXV0aG9yPkdy
YW1saWNoLCBULjwvYXV0aG9yPjxhdXRob3I+Qm9wYXJhaSwgTi48L2F1dGhvcj48YXV0aG9yPkxp
dSwgWS4gQy48L2F1dGhvcj48YXV0aG9yPk1jQ3VsbG91Z2gsIEEuIEouPC9hdXRob3I+PC9hdXRo
b3JzPjwvY29udHJpYnV0b3JzPjxhdXRoLWFkZHJlc3M+RGVwYXJ0bWVudCBvZiBHYXN0cm9lbnRl
cm9sb2d5LCBDbGV2ZWxhbmQsIE9oaW8sIFVTQS48L2F1dGgtYWRkcmVzcz48dGl0bGVzPjx0aXRs
ZT5Ob25hbGNvaG9saWMgZmF0dHkgbGl2ZXIgZGlzZWFzZTogYSBzcGVjdHJ1bSBvZiBjbGluaWNh
bCBhbmQgcGF0aG9sb2dpY2FsIHNldmVyaXR5PC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkdhc3Ry
b2VudGVyb2xvZ3k8L3NlY29uZGFyeS10aXRsZT48YWx0LXRpdGxlPkdhc3Ryb2VudGVyb2xvZ3k8
L2FsdC10aXRsZT48L3RpdGxlcz48cGFnZXM+MTQxMy05PC9wYWdlcz48dm9sdW1lPjExNjwvdm9s
dW1lPjxudW1iZXI+NjwvbnVtYmVyPjxrZXl3b3Jkcz48a2V5d29yZD5BZHVsdDwva2V5d29yZD48
a2V5d29yZD5BZ2VkPC9rZXl3b3JkPjxrZXl3b3JkPkJpb3BzeTwva2V5d29yZD48a2V5d29yZD5G
YXR0eSBMaXZlci9jbGFzc2lmaWNhdGlvbi9jb21wbGljYXRpb25zL21vcnRhbGl0eS8qcGF0aG9s
b2d5LypwaHlzaW9wYXRob2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+RmVtYWxlPC9rZXl3b3JkPjxr
ZXl3b3JkPkhlcGFjaXZpcnVzL2dlbmV0aWNzPC9rZXl3b3JkPjxrZXl3b3JkPkh1bWFuczwva2V5
d29yZD48a2V5d29yZD5Jcm9uL21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+TGl2ZXIvbWV0
YWJvbGlzbS9wYXRob2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+TGl2ZXIgQ2lycmhvc2lzL2NvbXBs
aWNhdGlvbnM8L2tleXdvcmQ+PGtleXdvcmQ+TG9uZ2l0dWRpbmFsIFN0dWRpZXM8L2tleXdvcmQ+
PGtleXdvcmQ+TWFsZTwva2V5d29yZD48a2V5d29yZD5NaWRkbGUgQWdlZDwva2V5d29yZD48a2V5
d29yZD5STkEsIE1lc3Nlbmdlci9tZXRhYm9saXNtPC9rZXl3b3JkPjxrZXl3b3JkPlJOQSwgVmly
YWwvbWV0YWJvbGlzbTwva2V5d29yZD48a2V5d29yZD5TdXJ2aXZhbCBBbmFseXNpczwva2V5d29y
ZD48L2tleXdvcmRzPjxkYXRlcz48eWVhcj4xOTk5PC95ZWFyPjxwdWItZGF0ZXM+PGRhdGU+SnVu
PC9kYXRlPjwvcHViLWRhdGVzPjwvZGF0ZXM+PGlzYm4+MDAxNi01MDg1IChQcmludCkmI3hEOzAw
MTYtNTA4NSAoTGlua2luZyk8L2lzYm4+PGFjY2Vzc2lvbi1udW0+MTAzNDg4MjU8L2FjY2Vzc2lv
bi1udW0+PHVybHM+PHJlbGF0ZWQtdXJscz48dXJsPmh0dHA6Ly93d3cubmNiaS5ubG0ubmloLmdv
di9wdWJtZWQvMTAzNDg4MjU8L3VybD48L3JlbGF0ZWQtdXJscz48L3VybHM+PC9yZWNvcmQ+PC9D
aXRlPjxDaXRlPjxBdXRob3I+UmFmaXE8L0F1dGhvcj48WWVhcj4yMDA5PC9ZZWFyPjxSZWNOdW0+
NTU8L1JlY051bT48cmVjb3JkPjxyZWMtbnVtYmVyPjU1PC9yZWMtbnVtYmVyPjxmb3JlaWduLWtl
eXM+PGtleSBhcHA9IkVOIiBkYi1pZD0iZnRlZnhlOXJtYTU1ZDRld3p2bXBzZXZhOXMyendhYXNz
cnJhIiB0aW1lc3RhbXA9IjAiPjU1PC9rZXk+PC9mb3JlaWduLWtleXM+PHJlZi10eXBlIG5hbWU9
IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBlPjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1
dGhvcj5SYWZpcSwgTi48L2F1dGhvcj48YXV0aG9yPkJhaSwgQy48L2F1dGhvcj48YXV0aG9yPkZh
bmcsIFkuPC9hdXRob3I+PGF1dGhvcj5TcmlzaG9yZCwgTS48L2F1dGhvcj48YXV0aG9yPk1jQ3Vs
bG91Z2gsIEEuPC9hdXRob3I+PGF1dGhvcj5HcmFtbGljaCwgVC48L2F1dGhvcj48YXV0aG9yPllv
dW5vc3NpLCBaLiBNLjwvYXV0aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48YXV0aC1hZGRy
ZXNzPkNlbnRlciBmb3IgTGl2ZXIgRGlzZWFzZXMsIElub3ZhIEhlYWx0aCBTeXN0ZW0sIEFubmFu
ZGFsZSwgVmlyZ2luaWEsIFVTQS48L2F1dGgtYWRkcmVzcz48dGl0bGVzPjx0aXRsZT5Mb25nLXRl
cm0gZm9sbG93LXVwIG9mIHBhdGllbnRzIHdpdGggbm9uYWxjb2hvbGljIGZhdHR5IGxpdmVyPC90
aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkNsaW4gR2FzdHJvZW50ZXJvbCBIZXBhdG9sPC9zZWNvbmRh
cnktdGl0bGU+PGFsdC10aXRsZT5DbGluaWNhbCBnYXN0cm9lbnRlcm9sb2d5IGFuZCBoZXBhdG9s
b2d5IDogdGhlIG9mZmljaWFsIGNsaW5pY2FsIHByYWN0aWNlIGpvdXJuYWwgb2YgdGhlIEFtZXJp
Y2FuIEdhc3Ryb2VudGVyb2xvZ2ljYWwgQXNzb2NpYXRpb248L2FsdC10aXRsZT48L3RpdGxlcz48
cGFnZXM+MjM0LTg8L3BhZ2VzPjx2b2x1bWU+Nzwvdm9sdW1lPjxudW1iZXI+MjwvbnVtYmVyPjxr
ZXl3b3Jkcz48a2V5d29yZD5BZHVsdDwva2V5d29yZD48a2V5d29yZD5CaW9wc3k8L2tleXdvcmQ+
PGtleXdvcmQ+KkRpc2Vhc2UgUHJvZ3Jlc3Npb248L2tleXdvcmQ+PGtleXdvcmQ+RmF0dHkgTGl2
ZXIvKmNvbXBsaWNhdGlvbnMvbW9ydGFsaXR5PC9rZXl3b3JkPjxrZXl3b3JkPkZlbWFsZTwva2V5
d29yZD48a2V5d29yZD5Gb2xsb3ctVXAgU3R1ZGllczwva2V5d29yZD48a2V5d29yZD5IdW1hbnM8
L2tleXdvcmQ+PGtleXdvcmQ+TWFsZTwva2V5d29yZD48a2V5d29yZD5NaWRkbGUgQWdlZDwva2V5
d29yZD48a2V5d29yZD5SaXNrIEZhY3RvcnM8L2tleXdvcmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHll
YXI+MjAwOTwveWVhcj48cHViLWRhdGVzPjxkYXRlPkZlYjwvZGF0ZT48L3B1Yi1kYXRlcz48L2Rh
dGVzPjxpc2JuPjE1NDItNzcxNCAoRWxlY3Ryb25pYykmI3hEOzE1NDItMzU2NSAoTGlua2luZyk8
L2lzYm4+PGFjY2Vzc2lvbi1udW0+MTkwNDk4MzE8L2FjY2Vzc2lvbi1udW0+PHVybHM+PHJlbGF0
ZWQtdXJscz48dXJsPmh0dHA6Ly93d3cubmNiaS5ubG0ubmloLmdvdi9wdWJtZWQvMTkwNDk4MzE8
L3VybD48L3JlbGF0ZWQtdXJscz48L3VybHM+PGVsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjEwLjEw
MTYvai5jZ2guMjAwOC4xMS4wMDU8L2VsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjwvcmVjb3JkPjwv
Q2l0ZT48L0VuZE5vdGU+AG==
ADDIN EN.CITE.DATA [49, 50]. Additionally, it has been anticipated to be the foremost reason for liver transplantation within the following few years ADDIN EN.CITE <EndNote><Cite><Author>Wong</Author><Year>2014</Year><RecNum>56</RecNum><DisplayText>[51]</DisplayText><record><rec-number>56</rec-number><foreign-keys><key app="EN" db-id="ftefxe9rma55d4ewzvmpseva9s2zwaassrra" timestamp="0">56</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Wong, R. J.</author><author>Cheung, R.</author><author>Ahmed, A.</author></authors></contributors><auth-address>Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA; Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA.</auth-address><titles><title>Nonalcoholic steatohepatitis is the most rapidly growing indication for liver transplantation in patients with hepatocellular carcinoma in the U.S</title><secondary-title>Hepatology</secondary-title><alt-title>Hepatology</alt-title></titles><pages>2188-95</pages><volume>59</volume><number>6</number><keywords><keyword>Aged</keyword><keyword>Carcinoma, Hepatocellular/epidemiology/*etiology/surgery</keyword><keyword>Fatty Liver/*complications/epidemiology/surgery</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Liver Neoplasms/epidemiology/*etiology/surgery</keyword><keyword>Liver Transplantation/*statistics & numerical data</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Non-alcoholic Fatty Liver Disease</keyword><keyword>Retrospective Studies</keyword><keyword>United States/epidemiology</keyword></keywords><dates><year>2014</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>1527-3350 (Electronic)
0270-9139 (Linking)</isbn><accession-num>24375711</accession-num><urls><related-urls><url>;[51]. A recent study emphasized that MALAT1, well-known for involvement in the progression of liver carcinoma may also play a key role in the occurrence of NASH as well as fibrosis in patients with Non-Alcoholic fatty liver disease (NAFLD) via a chemokine-mediated process ADDIN EN.CITE <EndNote><Cite><Author>Li</Author><Year>2015</Year><RecNum>57</RecNum><DisplayText>[52]</DisplayText><record><rec-number>57</rec-number><foreign-keys><key app="EN" db-id="ftefxe9rma55d4ewzvmpseva9s2zwaassrra" timestamp="0">57</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Li, C.</author><author>Chen, J.</author><author>Zhang, K.</author><author>Feng, B.</author><author>Wang, R.</author><author>Chen, L.</author></authors></contributors><auth-address>Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.</auth-address><titles><title>Progress and Prospects of Long Noncoding RNAs (lncRNAs) in Hepatocellular Carcinoma</title><secondary-title>Cell Physiol Biochem</secondary-title><alt-title>Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology</alt-title></titles><pages>423-34</pages><volume>36</volume><number>2</number><keywords><keyword>Animals</keyword><keyword>Biomarkers, Tumor/analysis/genetics</keyword><keyword>Carcinoma, Hepatocellular/diagnosis/*genetics/pathology</keyword><keyword>*Gene Expression Regulation, Neoplastic</keyword><keyword>Humans</keyword><keyword>Liver/*pathology</keyword><keyword>Liver Neoplasms/diagnosis/*genetics/pathology</keyword><keyword>Prognosis</keyword><keyword>RNA, Long Noncoding/analysis/*genetics</keyword></keywords><dates><year>2015</year></dates><isbn>1421-9778 (Electronic)
1015-8987 (Linking)</isbn><accession-num>25968300</accession-num><urls><related-urls><url>;[52]. Several lncRNA including nuclear paraspeckle assembly transcript 1, hepatocellular carcinoma upregulated lncRNA, and MALAT1 were tremendously expressed in liver fibrosis comparative to normal tissue. Moreover, the potential target of MALAT1 has been identified as C-X-C motif chemokine ligand 5 (CXCL5). However, CXCL5 showed discrepancy expression among different histologic cell types. Knockdown of MALAT1 by siRNA diminished protein levels and CXCL5 transcript by 30% and 50% respectively in HepG2 cells, indicating that MALAT1 plays a role in CXCL5 expression regulation ADDIN EN.CITE <EndNote><Cite><Author>Leti</Author><Year>2017</Year><RecNum>58</RecNum><DisplayText>[53]</DisplayText><record><rec-number>58</rec-number><foreign-keys><key app="EN" db-id="ftefxe9rma55d4ewzvmpseva9s2zwaassrra" timestamp="0">58</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Leti, F.</author><author>Legendre, C.</author><author>Still, C. D.</author><author>Chu, X.</author><author>Petrick, A.</author><author>Gerhard, G. S.</author><author>DiStefano, J. K.</author></authors></contributors><auth-address>National Jewish Health, Denver, Colo.
Translational Genomics Research Institute, Phoenix, Ariz.
Geisinger Obesity Institute, Danville, Pa.
Temple University School of Medicine, Philadelphia, Pa.
National Jewish Health, Denver, Colo. Electronic address: distefanoj@.</auth-address><titles><title>Altered expression of MALAT1 lncRNA in nonalcoholic steatohepatitis fibrosis regulates CXCL5 in hepatic stellate cells</title><secondary-title>Transl Res</secondary-title><alt-title>Translational research : the journal of laboratory and clinical medicine</alt-title></titles><pages>25-39 e21</pages><volume>190</volume><keywords><keyword>Chemokine CXCL5/genetics/*metabolism</keyword><keyword>Hepatic Stellate Cells/*metabolism</keyword><keyword>Humans</keyword><keyword>Liver Cirrhosis/*metabolism/pathology</keyword><keyword>Metabolic Networks and Pathways</keyword><keyword>Non-alcoholic Fatty Liver Disease/*metabolism/pathology</keyword><keyword>RNA, Long Noncoding/genetics/*metabolism</keyword><keyword>Transcriptome</keyword></keywords><dates><year>2017</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>1878-1810 (Electronic)
1878-1810 (Linking)</isbn><accession-num>28993096</accession-num><urls><related-urls><url>;[53]. Notable, hyperglycaemia control MALAT1 expression and treatment of high glucose with the hepatic cells resulted in increased levels of MALAT expression over time in HepG2 cells but no change in LX-2 cells ADDIN EN.CITE <EndNote><Cite><Author>Leti</Author><Year>2017</Year><RecNum>58</RecNum><DisplayText>[53]</DisplayText><record><rec-number>58</rec-number><foreign-keys><key app="EN" db-id="ftefxe9rma55d4ewzvmpseva9s2zwaassrra" timestamp="0">58</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Leti, F.</author><author>Legendre, C.</author><author>Still, C. D.</author><author>Chu, X.</author><author>Petrick, A.</author><author>Gerhard, G. S.</author><author>DiStefano, J. K.</author></authors></contributors><auth-address>National Jewish Health, Denver, Colo.
Translational Genomics Research Institute, Phoenix, Ariz.
Geisinger Obesity Institute, Danville, Pa.
Temple University School of Medicine, Philadelphia, Pa.
National Jewish Health, Denver, Colo. Electronic address: distefanoj@.</auth-address><titles><title>Altered expression of MALAT1 lncRNA in nonalcoholic steatohepatitis fibrosis regulates CXCL5 in hepatic stellate cells</title><secondary-title>Transl Res</secondary-title><alt-title>Translational research : the journal of laboratory and clinical medicine</alt-title></titles><pages>25-39 e21</pages><volume>190</volume><keywords><keyword>Chemokine CXCL5/genetics/*metabolism</keyword><keyword>Hepatic Stellate Cells/*metabolism</keyword><keyword>Humans</keyword><keyword>Liver Cirrhosis/*metabolism/pathology</keyword><keyword>Metabolic Networks and Pathways</keyword><keyword>Non-alcoholic Fatty Liver Disease/*metabolism/pathology</keyword><keyword>RNA, Long Noncoding/genetics/*metabolism</keyword><keyword>Transcriptome</keyword></keywords><dates><year>2017</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>1878-1810 (Electronic)
1878-1810 (Linking)</isbn><accession-num>28993096</accession-num><urls><related-urls><url>;[53]. High glucose, as well as type 2 diabetes, are associated with NAFLD severity along with development of hepatic inflammation and fibrosis PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5GYXJyZWxsPC9BdXRob3I+PFllYXI+MjAwNjwvWWVhcj48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 EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5GYXJyZWxsPC9BdXRob3I+PFllYXI+MjAwNjwvWWVhcj48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 EN.CITE.DATA [54-56]. These conclusions uphold a role for CXCL5 in the pathogenesis of liver disease, possibly through a MALAT1-mediated mechanism. Further studies will be required on the association between MALAT1 and CXCL5. Diabetic Gastropathy Gastroparesis is a symptomatic disorder of the stomach defined by delayed emptying of ingested food particles. DM along with idiopathic factors contributes nearly 60% of gastroparesis cases PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BbGk8L0F1dGhvcj48WWVhcj4yMDA3PC9ZZWFyPjxSZWNO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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BbGk8L0F1dGhvcj48WWVhcj4yMDA3PC9ZZWFyPjxSZWNO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ADDIN EN.CITE.DATA [57]. Previous studies demonstrated that gastrointestinal symptoms occur in about 75% of the diabetic cases, while approximately 30-50% of these cases were due to diabetic gastropathy PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Hb3lhbDwvQXV0aG9yPjxZZWFyPjE5NzE8L1llYXI+PFJl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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Hb3lhbDwvQXV0aG9yPjxZZWFyPjE5NzE8L1llYXI+PFJl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ADDIN EN.CITE.DATA [58-60]. However, the prevalence of gastroparesis in diabetes mellitus type 1 (T1DM) varies considerably. In addition, 40% of T1DM patients were diagnosed with gastroparesis in tertiary centres ADDIN EN.CITE <EndNote><Cite><Author>De Block</Author><Year>2006</Year><RecNum>66</RecNum><DisplayText>[60]</DisplayText><record><rec-number>66</rec-number><foreign-keys><key app="EN" db-id="ftefxe9rma55d4ewzvmpseva9s2zwaassrra" timestamp="0">66</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>De Block, C. E.</author><author>De Leeuw, I. H.</author><author>Pelckmans, P. A.</author><author>Van Gaal, L. F.</author></authors></contributors><auth-address>Department of Diabetology & Endocrinology, Faculty of Medicine, University of Antwerp, University Hospital Antwerp (UZA), Wilrijkstraat 10, B-2650 Edegem, Belgium. christophe.deblock@ua.ac.be</auth-address><titles><title>Current concepts in gastric motility in diabetes mellitus</title><secondary-title>Curr Diabetes Rev</secondary-title><alt-title>Current diabetes reviews</alt-title></titles><pages>113-30</pages><volume>2</volume><number>1</number><keywords><keyword>Diabetes Complications/epidemiology/*physiopathology/surgery</keyword><keyword>Diabetes Mellitus/*physiopathology</keyword><keyword>Diabetes Mellitus, Type 1/complications</keyword><keyword>Diabetes Mellitus, Type 2/complications</keyword><keyword>Duodenum/physiology/physiopathology</keyword><keyword>Eating</keyword><keyword>Gastrectomy</keyword><keyword>Gastrointestinal Motility/*physiology</keyword><keyword>Gastroparesis/*epidemiology</keyword><keyword>Humans</keyword><keyword>Jejunum/surgery</keyword><keyword>Stomach/physiology/physiopathology</keyword></keywords><dates><year>2006</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>1573-3998 (Print)
1573-3998 (Linking)</isbn><accession-num>18220621</accession-num><urls><related-urls><url>;[60]. Recently, lncRNA MALAT1 was developed as a probable regulator in the pathogenesis of DGP. Smooth muscle cells (SMC) contractility marker proteins were found to be decreased in gastric models of DM mouse and MALAT1 expression was higher in DGP rat model. Secondly, MALAT1 was over-expressed in the adjacent health tissues taken from diabetic gastric cancer patients with DGP. In human gastrointestinal SMCs, high sugar levels augmented the MALAT1 expression. MALAT ablation shortened the cell viability, suppressed impending of the cell migration and carried cell death in human gastric SMCs preserved with high glucose. And, MALAT1 suppression induced α-SMA and SM myosin heavy chains expression, prompting the SMCs to express contractility markers ADDIN EN.CITE <EndNote><Cite><Author>Horvath</Author><Year>2006</Year><RecNum>67</RecNum><DisplayText>[61]</DisplayText><record><rec-number>67</rec-number><foreign-keys><key app="EN" db-id="ftefxe9rma55d4ewzvmpseva9s2zwaassrra" timestamp="0">67</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Horvath, V. J.</author><author>Vittal, H.</author><author>Lorincz, A.</author><author>Chen, H.</author><author>Almeida-Porada, G.</author><author>Redelman, D.</author><author>Ordog, T.</author></authors></contributors><auth-address>Department of Physiology and Cell Biology, University of Nevada, Reno, Nevada, USA.</auth-address><titles><title>Reduced stem cell factor links smooth myopathy and loss of interstitial cells of cajal in murine diabetic gastroparesis</title><secondary-title>Gastroenterology</secondary-title><alt-title>Gastroenterology</alt-title></titles><pages>759-70</pages><volume>130</volume><number>3</number><keywords><keyword>Animals</keyword><keyword>Coiled Bodies/*pathology</keyword><keyword>Diabetic Neuropathies/*etiology/pathology</keyword><keyword>Female</keyword><keyword>Gastroparesis/*etiology/pathology</keyword><keyword>Insulin-Like Growth Factor I/genetics</keyword><keyword>Mice</keyword><keyword>Mice, Inbred BALB C</keyword><keyword>Mice, Inbred NOD</keyword><keyword>Muscle, Smooth/*pathology</keyword><keyword>RNA, Messenger/analysis</keyword><keyword>Receptor, Insulin/genetics</keyword><keyword>Stem Cell Factor/analysis/*physiology</keyword></keywords><dates><year>2006</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0016-5085 (Print)
0016-5085 (Linking)</isbn><accession-num>16530517</accession-num><urls><related-urls><url>;[61]. Hence, MALAT1 was associated with the progression of DGP leading to phenotype alteration and influencing normal cellular processes of smooth muscle cells. However, more intensive laboratories works are necessary to the highlight the precise mechanism and function of lncRNA MALAT1 in SMC phenotype switch.Diabetic Kidney DiseaseDiabetic kidney disease is an advancing condition that progresses secondary to DM PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CaWNodTwvQXV0aG9yPjxZZWFyPjIwMDk8L1llYXI+PFJl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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CaWNodTwvQXV0aG9yPjxZZWFyPjIwMDk8L1llYXI+PFJl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ADDIN EN.CITE.DATA [62]. It is the principal cause of chronic renal failure accounting for nearly 50% of all end-stage renal disease PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BZmthcmlhbjwvQXV0aG9yPjxZZWFyPjIwMTM8L1llYXI+
PFJlY051bT42OTwvUmVjTnVtPjxEaXNwbGF5VGV4dD5bNjMsIDY0XTwvRGlzcGxheVRleHQ+PHJl
Y29yZD48cmVjLW51bWJlcj42OTwvcmVjLW51bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJF
TiIgZGItaWQ9ImZ0ZWZ4ZTlybWE1NWQ0ZXd6dm1wc2V2YTlzMnp3YWFzc3JyYSIgdGltZXN0YW1w
PSIwIj42OTwva2V5PjwvZm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJKb3VybmFsIEFydGlj
bGUiPjE3PC9yZWYtdHlwZT48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+QWZrYXJpYW4s
IE0uPC9hdXRob3I+PGF1dGhvcj5TYWNocywgTS4gQy48L2F1dGhvcj48YXV0aG9yPktlc3RlbmJh
dW0sIEIuPC9hdXRob3I+PGF1dGhvcj5IaXJzY2gsIEkuIEIuPC9hdXRob3I+PGF1dGhvcj5UdXR0
bGUsIEsuIFIuPC9hdXRob3I+PGF1dGhvcj5IaW1tZWxmYXJiLCBKLjwvYXV0aG9yPjxhdXRob3I+
ZGUgQm9lciwgSS4gSC48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgtYWRk
cmVzcz5LaWRuZXkgUmVzZWFyY2ggSW5zdGl0dXRlIGFuZCBEaXZpc2lvbiBvZiBOZXBocm9sb2d5
LCBEZXBhcnRtZW50IG9mIE1lZGljaW5lLCBVbml2ZXJzaXR5IG9mIFdhc2hpbmd0b24sIFNlYXR0
bGUsIFdBIDk4MDE0LCBVU0EuIGFma2FyaWFuQHUud2FzaGluZ3Rvbi5lZHU8L2F1dGgtYWRkcmVz
cz48dGl0bGVzPjx0aXRsZT5LaWRuZXkgZGlzZWFzZSBhbmQgaW5jcmVhc2VkIG1vcnRhbGl0eSBy
aXNrIGluIHR5cGUgMiBkaWFiZXRlczwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5KIEFtIFNvYyBO
ZXBocm9sPC9zZWNvbmRhcnktdGl0bGU+PGFsdC10aXRsZT5Kb3VybmFsIG9mIHRoZSBBbWVyaWNh
biBTb2NpZXR5IG9mIE5lcGhyb2xvZ3kgOiBKQVNOPC9hbHQtdGl0bGU+PC90aXRsZXM+PHBhZ2Vz
PjMwMi04PC9wYWdlcz48dm9sdW1lPjI0PC92b2x1bWU+PG51bWJlcj4yPC9udW1iZXI+PGtleXdv
cmRzPjxrZXl3b3JkPkFkdWx0PC9rZXl3b3JkPjxrZXl3b3JkPkFnZWQ8L2tleXdvcmQ+PGtleXdv
cmQ+QWxidW1pbnVyaWEvKm1vcnRhbGl0eTwva2V5d29yZD48a2V5d29yZD5EaWFiZXRlcyBNZWxs
aXR1cywgVHlwZSAyLyptb3J0YWxpdHk8L2tleXdvcmQ+PGtleXdvcmQ+RGlhYmV0aWMgTmVwaHJv
cGF0aGllcy8qbW9ydGFsaXR5PC9rZXl3b3JkPjxrZXl3b3JkPkZlbWFsZTwva2V5d29yZD48a2V5
d29yZD5Gb2xsb3ctVXAgU3R1ZGllczwva2V5d29yZD48a2V5d29yZD5HbG9tZXJ1bGFyIEZpbHRy
YXRpb24gUmF0ZTwva2V5d29yZD48a2V5d29yZD5IdW1hbnM8L2tleXdvcmQ+PGtleXdvcmQ+TWFs
ZTwva2V5d29yZD48a2V5d29yZD5NaWRkbGUgQWdlZDwva2V5d29yZD48a2V5d29yZD5OdXRyaXRp
b24gU3VydmV5cy9zdGF0aXN0aWNzICZhbXA7IG51bWVyaWNhbCBkYXRhPC9rZXl3b3JkPjxrZXl3
b3JkPlByZXZhbGVuY2U8L2tleXdvcmQ+PGtleXdvcmQ+UmlzayBGYWN0b3JzPC9rZXl3b3JkPjxr
ZXl3b3JkPlVuaXRlZCBTdGF0ZXMvZXBpZGVtaW9sb2d5PC9rZXl3b3JkPjwva2V5d29yZHM+PGRh
dGVzPjx5ZWFyPjIwMTM8L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5GZWI8L2RhdGU+PC9wdWItZGF0
ZXM+PC9kYXRlcz48aXNibj4xNTMzLTM0NTAgKEVsZWN0cm9uaWMpJiN4RDsxMDQ2LTY2NzMgKExp
bmtpbmcpPC9pc2JuPjxhY2Nlc3Npb24tbnVtPjIzMzYyMzE0PC9hY2Nlc3Npb24tbnVtPjx1cmxz
PjxyZWxhdGVkLXVybHM+PHVybD5odHRwOi8vd3d3Lm5jYmkubmxtLm5paC5nb3YvcHVibWVkLzIz
MzYyMzE0PC91cmw+PC9yZWxhdGVkLXVybHM+PC91cmxzPjxjdXN0b20yPjM1NTk0ODY8L2N1c3Rv
bTI+PGVsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjEwLjE2ODEvQVNOLjIwMTIwNzA3MTg8L2VsZWN0
cm9uaWMtcmVzb3VyY2UtbnVtPjwvcmVjb3JkPjwvQ2l0ZT48Q2l0ZT48QXV0aG9yPkthbndhcjwv
QXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+PFJlY051bT43MDwvUmVjTnVtPjxyZWNvcmQ+PHJlYy1u
dW1iZXI+NzA8L3JlYy1udW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0iRU4iIGRiLWlkPSJm
dGVmeGU5cm1hNTVkNGV3enZtcHNldmE5czJ6d2Fhc3NycmEiIHRpbWVzdGFtcD0iMCI+NzA8L2tl
eT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVm
LXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPkthbndhciwgWS4gUy48L2F1dGhv
cj48YXV0aG9yPlN1biwgTC48L2F1dGhvcj48YXV0aG9yPlhpZSwgUC48L2F1dGhvcj48YXV0aG9y
PkxpdSwgRi4gWS48L2F1dGhvcj48YXV0aG9yPkNoZW4sIFMuPC9hdXRob3I+PC9hdXRob3JzPjwv
Y29udHJpYnV0b3JzPjxhdXRoLWFkZHJlc3M+RGVwYXJ0bWVudHMgb2YgUGF0aG9sb2d5LCBOb3J0
aHdlc3Rlcm4gVW5pdmVyc2l0eSBTY2hvb2wgb2YgTWVkaWNpbmUsIENoaWNhZ28sIElsbGlub2lz
IDYwNjExLCBVU0EuIHkta2Fud2FyQG5vcnRod2VzdGVybi5lZHU8L2F1dGgtYWRkcmVzcz48dGl0
bGVzPjx0aXRsZT5BIGdsaW1wc2Ugb2YgdmFyaW91cyBwYXRob2dlbmV0aWMgbWVjaGFuaXNtcyBv
ZiBkaWFiZXRpYyBuZXBocm9wYXRoeTwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5Bbm51IFJldiBQ
YXRob2w8L3NlY29uZGFyeS10aXRsZT48YWx0LXRpdGxlPkFubnVhbCByZXZpZXcgb2YgcGF0aG9s
b2d5PC9hbHQtdGl0bGU+PC90aXRsZXM+PHBhZ2VzPjM5NS00MjM8L3BhZ2VzPjx2b2x1bWU+Njwv
dm9sdW1lPjxrZXl3b3Jkcz48a2V5d29yZD4qRGlhYmV0aWMgTmVwaHJvcGF0aGllcy9ldGlvbG9n
eS9wYXRob2xvZ3kvcGh5c2lvcGF0aG9sb2d5PC9rZXl3b3JkPjxrZXl3b3JkPkh1bWFuczwva2V5
d29yZD48a2V5d29yZD5LaWRuZXkvKnBhdGhvbG9neS8qcGh5c2lvcGF0aG9sb2d5PC9rZXl3b3Jk
Pjwva2V5d29yZHM+PGRhdGVzPjx5ZWFyPjIwMTE8L3llYXI+PC9kYXRlcz48aXNibj4xNTUzLTQw
MTQgKEVsZWN0cm9uaWMpJiN4RDsxNTUzLTQwMDYgKExpbmtpbmcpPC9pc2JuPjxhY2Nlc3Npb24t
bnVtPjIxMjYxNTIwPC9hY2Nlc3Npb24tbnVtPjx1cmxzPjxyZWxhdGVkLXVybHM+PHVybD5odHRw
Oi8vd3d3Lm5jYmkubmxtLm5paC5nb3YvcHVibWVkLzIxMjYxNTIwPC91cmw+PC9yZWxhdGVkLXVy
bHM+PC91cmxzPjxjdXN0b20yPjM3MDAzNzk8L2N1c3RvbTI+PGVsZWN0cm9uaWMtcmVzb3VyY2Ut
bnVtPjEwLjExNDYvYW5udXJldi5wYXRob2wuNC4xMTA4MDcuMDkyMTUwPC9lbGVjdHJvbmljLXJl
c291cmNlLW51bT48L3JlY29yZD48L0NpdGU+PC9FbmROb3RlPgB=
ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BZmthcmlhbjwvQXV0aG9yPjxZZWFyPjIwMTM8L1llYXI+
PFJlY051bT42OTwvUmVjTnVtPjxEaXNwbGF5VGV4dD5bNjMsIDY0XTwvRGlzcGxheVRleHQ+PHJl
Y29yZD48cmVjLW51bWJlcj42OTwvcmVjLW51bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJF
TiIgZGItaWQ9ImZ0ZWZ4ZTlybWE1NWQ0ZXd6dm1wc2V2YTlzMnp3YWFzc3JyYSIgdGltZXN0YW1w
PSIwIj42OTwva2V5PjwvZm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJKb3VybmFsIEFydGlj
bGUiPjE3PC9yZWYtdHlwZT48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+QWZrYXJpYW4s
IE0uPC9hdXRob3I+PGF1dGhvcj5TYWNocywgTS4gQy48L2F1dGhvcj48YXV0aG9yPktlc3RlbmJh
dW0sIEIuPC9hdXRob3I+PGF1dGhvcj5IaXJzY2gsIEkuIEIuPC9hdXRob3I+PGF1dGhvcj5UdXR0
bGUsIEsuIFIuPC9hdXRob3I+PGF1dGhvcj5IaW1tZWxmYXJiLCBKLjwvYXV0aG9yPjxhdXRob3I+
ZGUgQm9lciwgSS4gSC48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgtYWRk
cmVzcz5LaWRuZXkgUmVzZWFyY2ggSW5zdGl0dXRlIGFuZCBEaXZpc2lvbiBvZiBOZXBocm9sb2d5
LCBEZXBhcnRtZW50IG9mIE1lZGljaW5lLCBVbml2ZXJzaXR5IG9mIFdhc2hpbmd0b24sIFNlYXR0
bGUsIFdBIDk4MDE0LCBVU0EuIGFma2FyaWFuQHUud2FzaGluZ3Rvbi5lZHU8L2F1dGgtYWRkcmVz
cz48dGl0bGVzPjx0aXRsZT5LaWRuZXkgZGlzZWFzZSBhbmQgaW5jcmVhc2VkIG1vcnRhbGl0eSBy
aXNrIGluIHR5cGUgMiBkaWFiZXRlczwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5KIEFtIFNvYyBO
ZXBocm9sPC9zZWNvbmRhcnktdGl0bGU+PGFsdC10aXRsZT5Kb3VybmFsIG9mIHRoZSBBbWVyaWNh
biBTb2NpZXR5IG9mIE5lcGhyb2xvZ3kgOiBKQVNOPC9hbHQtdGl0bGU+PC90aXRsZXM+PHBhZ2Vz
PjMwMi04PC9wYWdlcz48dm9sdW1lPjI0PC92b2x1bWU+PG51bWJlcj4yPC9udW1iZXI+PGtleXdv
cmRzPjxrZXl3b3JkPkFkdWx0PC9rZXl3b3JkPjxrZXl3b3JkPkFnZWQ8L2tleXdvcmQ+PGtleXdv
cmQ+QWxidW1pbnVyaWEvKm1vcnRhbGl0eTwva2V5d29yZD48a2V5d29yZD5EaWFiZXRlcyBNZWxs
aXR1cywgVHlwZSAyLyptb3J0YWxpdHk8L2tleXdvcmQ+PGtleXdvcmQ+RGlhYmV0aWMgTmVwaHJv
cGF0aGllcy8qbW9ydGFsaXR5PC9rZXl3b3JkPjxrZXl3b3JkPkZlbWFsZTwva2V5d29yZD48a2V5
d29yZD5Gb2xsb3ctVXAgU3R1ZGllczwva2V5d29yZD48a2V5d29yZD5HbG9tZXJ1bGFyIEZpbHRy
YXRpb24gUmF0ZTwva2V5d29yZD48a2V5d29yZD5IdW1hbnM8L2tleXdvcmQ+PGtleXdvcmQ+TWFs
ZTwva2V5d29yZD48a2V5d29yZD5NaWRkbGUgQWdlZDwva2V5d29yZD48a2V5d29yZD5OdXRyaXRp
b24gU3VydmV5cy9zdGF0aXN0aWNzICZhbXA7IG51bWVyaWNhbCBkYXRhPC9rZXl3b3JkPjxrZXl3
b3JkPlByZXZhbGVuY2U8L2tleXdvcmQ+PGtleXdvcmQ+UmlzayBGYWN0b3JzPC9rZXl3b3JkPjxr
ZXl3b3JkPlVuaXRlZCBTdGF0ZXMvZXBpZGVtaW9sb2d5PC9rZXl3b3JkPjwva2V5d29yZHM+PGRh
dGVzPjx5ZWFyPjIwMTM8L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5GZWI8L2RhdGU+PC9wdWItZGF0
ZXM+PC9kYXRlcz48aXNibj4xNTMzLTM0NTAgKEVsZWN0cm9uaWMpJiN4RDsxMDQ2LTY2NzMgKExp
bmtpbmcpPC9pc2JuPjxhY2Nlc3Npb24tbnVtPjIzMzYyMzE0PC9hY2Nlc3Npb24tbnVtPjx1cmxz
PjxyZWxhdGVkLXVybHM+PHVybD5odHRwOi8vd3d3Lm5jYmkubmxtLm5paC5nb3YvcHVibWVkLzIz
MzYyMzE0PC91cmw+PC9yZWxhdGVkLXVybHM+PC91cmxzPjxjdXN0b20yPjM1NTk0ODY8L2N1c3Rv
bTI+PGVsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjEwLjE2ODEvQVNOLjIwMTIwNzA3MTg8L2VsZWN0
cm9uaWMtcmVzb3VyY2UtbnVtPjwvcmVjb3JkPjwvQ2l0ZT48Q2l0ZT48QXV0aG9yPkthbndhcjwv
QXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+PFJlY051bT43MDwvUmVjTnVtPjxyZWNvcmQ+PHJlYy1u
dW1iZXI+NzA8L3JlYy1udW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0iRU4iIGRiLWlkPSJm
dGVmeGU5cm1hNTVkNGV3enZtcHNldmE5czJ6d2Fhc3NycmEiIHRpbWVzdGFtcD0iMCI+NzA8L2tl
eT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVm
LXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPkthbndhciwgWS4gUy48L2F1dGhv
cj48YXV0aG9yPlN1biwgTC48L2F1dGhvcj48YXV0aG9yPlhpZSwgUC48L2F1dGhvcj48YXV0aG9y
PkxpdSwgRi4gWS48L2F1dGhvcj48YXV0aG9yPkNoZW4sIFMuPC9hdXRob3I+PC9hdXRob3JzPjwv
Y29udHJpYnV0b3JzPjxhdXRoLWFkZHJlc3M+RGVwYXJ0bWVudHMgb2YgUGF0aG9sb2d5LCBOb3J0
aHdlc3Rlcm4gVW5pdmVyc2l0eSBTY2hvb2wgb2YgTWVkaWNpbmUsIENoaWNhZ28sIElsbGlub2lz
IDYwNjExLCBVU0EuIHkta2Fud2FyQG5vcnRod2VzdGVybi5lZHU8L2F1dGgtYWRkcmVzcz48dGl0
bGVzPjx0aXRsZT5BIGdsaW1wc2Ugb2YgdmFyaW91cyBwYXRob2dlbmV0aWMgbWVjaGFuaXNtcyBv
ZiBkaWFiZXRpYyBuZXBocm9wYXRoeTwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5Bbm51IFJldiBQ
YXRob2w8L3NlY29uZGFyeS10aXRsZT48YWx0LXRpdGxlPkFubnVhbCByZXZpZXcgb2YgcGF0aG9s
b2d5PC9hbHQtdGl0bGU+PC90aXRsZXM+PHBhZ2VzPjM5NS00MjM8L3BhZ2VzPjx2b2x1bWU+Njwv
dm9sdW1lPjxrZXl3b3Jkcz48a2V5d29yZD4qRGlhYmV0aWMgTmVwaHJvcGF0aGllcy9ldGlvbG9n
eS9wYXRob2xvZ3kvcGh5c2lvcGF0aG9sb2d5PC9rZXl3b3JkPjxrZXl3b3JkPkh1bWFuczwva2V5
d29yZD48a2V5d29yZD5LaWRuZXkvKnBhdGhvbG9neS8qcGh5c2lvcGF0aG9sb2d5PC9rZXl3b3Jk
Pjwva2V5d29yZHM+PGRhdGVzPjx5ZWFyPjIwMTE8L3llYXI+PC9kYXRlcz48aXNibj4xNTUzLTQw
MTQgKEVsZWN0cm9uaWMpJiN4RDsxNTUzLTQwMDYgKExpbmtpbmcpPC9pc2JuPjxhY2Nlc3Npb24t
bnVtPjIxMjYxNTIwPC9hY2Nlc3Npb24tbnVtPjx1cmxzPjxyZWxhdGVkLXVybHM+PHVybD5odHRw
Oi8vd3d3Lm5jYmkubmxtLm5paC5nb3YvcHVibWVkLzIxMjYxNTIwPC91cmw+PC9yZWxhdGVkLXVy
bHM+PC91cmxzPjxjdXN0b20yPjM3MDAzNzk8L2N1c3RvbTI+PGVsZWN0cm9uaWMtcmVzb3VyY2Ut
bnVtPjEwLjExNDYvYW5udXJldi5wYXRob2wuNC4xMTA4MDcuMDkyMTUwPC9lbGVjdHJvbmljLXJl
c291cmNlLW51bT48L3JlY29yZD48L0NpdGU+PC9FbmROb3RlPgB=
ADDIN EN.CITE.DATA [63, 64]. Existing treatment modalities are directed towards the decreasing blood pressure as well as blood sugar to reduce albuminuria and slow disease progression. However, in the majority of cases, there are no reliable methods to prevent the development of diabetic kidney disease and chronic renal failure. Thus, there is an urgent need for therapeutic targets for drug development as well as diagnostic markers for clinical treatments to prevent the development and progression of diabetic kidney disease. MALAT1 was notably highly expressed?in kidney tissues from C57BL/6 mice with streptozocin-induced diabetic kidney disease. Hu et al. reported that early interfering with MALAT1 siRNA partly re-established podocytes function as well as proscribed b-catenin nuclear accumulation and SRSF1 overexpression. Furthermore, b-catenin was involved in MALAT1 transcription by binding to the promotor region of MALAT1; b-catenin knock-down also decreased MALAT1 levels PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IdTwvQXV0aG9yPjxZZWFyPjIwMTc8L1llYXI+PFJlY051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 EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IdTwvQXV0aG9yPjxZZWFyPjIwMTc8L1llYXI+PFJlY051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 EN.CITE.DATA [65]. In addition, Li et al. reported that with an increase in MALAT1 expression there was a decrease in miR-23c in streptozotocin-induced diabetic rats as well as in high-glucose-treated HK-2 cells. Down-regulation of MALAT1 inhibited the expression of ELAVL1, NLRP3, Caspase-1 as well as the pro-inflammatory cytokine IL-1β and up-regulated the expression of miR-23c. Besides, luciferase assays revealed that the expression of MALAT1 antagonized the effect of miR-23c on the down-regulation of its target ELAVL1 and inhibited hyperglycemia-induced cell pyroptosis PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MaTwvQXV0aG9yPjxZZWFyPjIwMTc8L1llYXI+PFJlY051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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MaTwvQXV0aG9yPjxZZWFyPjIwMTc8L1llYXI+PFJlY051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ADDIN EN.CITE.DATA [66]. In another study, Wu et al., showed that expression level of MALAT1, as well as its downstream target SAA3, was considerably down-regulated in renal tissues after bariatric surgery in rats, which in turn reduced the expression of the pro-inflammatory cytokines IL-6 and TNF-α. Knockdown of MALAT1 in HK-2 cell lines further confirmed that expression levels of SAA3, IL-6, and TNF-α were regulated by MALAT1 under both low- and high-glucose conditions ADDIN EN.CITE <EndNote><Cite><Author>Wu</Author><Year>2018</Year><RecNum>73</RecNum><DisplayText>[67]</DisplayText><record><rec-number>73</rec-number><foreign-keys><key app="EN" db-id="ftefxe9rma55d4ewzvmpseva9s2zwaassrra" timestamp="0">73</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Wu, D.</author><author>Cheng, Y. G.</author><author>Huang, X.</author><author>Zhong, M. W.</author><author>Liu, S. Z.</author><author>Hu, S. Y.</author></authors></contributors><auth-address>Department of General Surgery, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, 250012, People's Republic of China.
Department of General Surgery, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, 250012, People's Republic of China. liushaozhuang@sdu..</auth-address><titles><title>Downregulation of lncRNA MALAT1 contributes to renal functional improvement after duodenal-jejunal bypass in a diabetic rat model</title><secondary-title>J Physiol Biochem</secondary-title><alt-title>Journal of physiology and biochemistry</alt-title></titles><pages>431-439</pages><volume>74</volume><number>3</number><dates><year>2018</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1877-8755 (Electronic)
1138-7548 (Linking)</isbn><accession-num>29781038</accession-num><urls><related-urls><url>;[67]. Therefore, MALAT1 plays a key pivotal role in diabetic nephropathy and recognizing this mechanism may ultimately contribute to the progress of novel lncRNA-based therapeutic strategies for the management of diabetic kidney disease.Gestational Diabetes MellitusGestational diabetes mellitus (GDM) is a type of diabetes characterized by glucose intolerance with onset during pregnancy, resulting in high blood sugar level with varying severity ADDIN EN.CITE <EndNote><Cite><Author>Metzger</Author><Year>1998</Year><RecNum>74</RecNum><DisplayText>[68]</DisplayText><record><rec-number>74</rec-number><foreign-keys><key app="EN" db-id="ftefxe9rma55d4ewzvmpseva9s2zwaassrra" timestamp="0">74</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Metzger, B. E.</author><author>Coustan, D. R.</author></authors></contributors><auth-address>Northwestern University Medical School, Chicago, Illionois 60611, USA. bem@nwu.edu</auth-address><titles><title>Summary and recommendations of the Fourth International Workshop-Conference on Gestational Diabetes Mellitus. The Organizing Committee</title><secondary-title>Diabetes Care</secondary-title><alt-title>Diabetes care</alt-title></titles><pages>B161-7</pages><volume>21 Suppl 2</volume><keywords><keyword>*Diabetes, Gestational/diagnosis/epidemiology/therapy</keyword><keyword>Female</keyword><keyword>Glucose Intolerance</keyword><keyword>Humans</keyword><keyword>Infant, Newborn</keyword><keyword>Pregnancy</keyword><keyword>Pregnancy Outcome</keyword><keyword>Prevalence</keyword><keyword>United States/epidemiology</keyword></keywords><dates><year>1998</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0149-5992 (Print)
0149-5992 (Linking)</isbn><accession-num>9704245</accession-num><urls><related-urls><url>;[68]. Recent studies had shown that one in seven births were affected by this disease, regardless of the reduced global number of cases which has fallen to 21.0 million ADDIN EN.CITE <EndNote><Cite><Author>Metzger</Author><Year>1998</Year><RecNum>75</RecNum><DisplayText>[68]</DisplayText><record><rec-number>75</rec-number><foreign-keys><key app="EN" db-id="ftefxe9rma55d4ewzvmpseva9s2zwaassrra" timestamp="0">75</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Metzger, B. E.</author><author>Coustan, D. R.</author></authors></contributors><auth-address>Northwestern University Medical School, Chicago, Illionois 60611, USA. bem@nwu.edu</auth-address><titles><title>Summary and recommendations of the Fourth International Workshop-Conference on Gestational Diabetes Mellitus. The Organizing Committee</title><secondary-title>Diabetes Care</secondary-title><alt-title>Diabetes care</alt-title></titles><pages>B161-7</pages><volume>21 Suppl 2</volume><keywords><keyword>*Diabetes, Gestational/diagnosis/epidemiology/therapy</keyword><keyword>Female</keyword><keyword>Glucose Intolerance</keyword><keyword>Humans</keyword><keyword>Infant, Newborn</keyword><keyword>Pregnancy</keyword><keyword>Pregnancy Outcome</keyword><keyword>Prevalence</keyword><keyword>United States/epidemiology</keyword></keywords><dates><year>1998</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0149-5992 (Print)
0149-5992 (Linking)</isbn><accession-num>9704245</accession-num><urls><related-urls><url>;[68]. Likewise, other type of hyperglycaemias, GDM also redirects a functional difference between a person’s insulin secretion and insulin demand ADDIN EN.CITE <EndNote><Cite><Author>Buchanan</Author><Year>2007</Year><RecNum>76</RecNum><DisplayText>[69]</DisplayText><record><rec-number>76</rec-number><foreign-keys><key app="EN" db-id="ftefxe9rma55d4ewzvmpseva9s2zwaassrra" timestamp="0">76</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Buchanan, T. A.</author><author>Xiang, A.</author><author>Kjos, S. L.</author><author>Watanabe, R.</author></authors></contributors><auth-address>Departments of Medicine, Obstetrics and Gynecology, and Physiology and Biophysics, University of Southern California Keck School of Medicine, Los Angeles, California, USA. buchanan@usc.edu</auth-address><titles><title>What is gestational diabetes?</title><secondary-title>Diabetes Care</secondary-title><alt-title>Diabetes care</alt-title></titles><pages>S105-11</pages><volume>30 Suppl 2</volume><keywords><keyword>Blood Glucose/*metabolism</keyword><keyword>Diabetes Mellitus/*etiology/prevention & control</keyword><keyword>*Diabetes, Gestational/diagnosis/etiology/therapy</keyword><keyword>Female</keyword><keyword>Glucose Intolerance</keyword><keyword>Humans</keyword><keyword>Pregnancy</keyword></keywords><dates><year>2007</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>1935-5548 (Electronic)
0149-5992 (Linking)</isbn><accession-num>17596457</accession-num><urls><related-urls><url>;[69]. GDM prevalence is excessive in summer, perhaps reflecting an association between blood glucose levels and temperature. The exact mechanism by which temperature may influence glucose metabolism in pregnancy remains uncertain PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5SZXRuYWthcmFuPC9BdXRob3I+PFllYXI+MjAxODwvWWVh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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5SZXRuYWthcmFuPC9BdXRob3I+PFllYXI+MjAxODwvWWVh
cj48UmVjTnVtPjc3PC9SZWNOdW0+PERpc3BsYXlUZXh0Pls3MF08L0Rpc3BsYXlUZXh0PjxyZWNv
cmQ+PHJlYy1udW1iZXI+Nzc8L3JlYy1udW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0iRU4i
IGRiLWlkPSJmdGVmeGU5cm1hNTVkNGV3enZtcHNldmE5czJ6d2Fhc3NycmEiIHRpbWVzdGFtcD0i
MCI+Nzc8L2tleT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xl
Ij4xNzwvcmVmLXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPlJldG5ha2FyYW4s
IFIuPC9hdXRob3I+PGF1dGhvcj5ZZSwgQy48L2F1dGhvcj48YXV0aG9yPktyYW1lciwgQy4gSy48
L2F1dGhvcj48YXV0aG9yPkhhbmxleSwgQS4gSi48L2F1dGhvcj48YXV0aG9yPkNvbm5lbGx5LCBQ
LiBXLjwvYXV0aG9yPjxhdXRob3I+U2VybWVyLCBNLjwvYXV0aG9yPjxhdXRob3I+WmlubWFuLCBC
LjwvYXV0aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48YXV0aC1hZGRyZXNzPkxlYWRlcnNo
aXAgU2luYWkgQ2VudHJlIGZvciBEaWFiZXRlcywgTW91bnQgU2luYWkgSG9zcGl0YWwsIDYwIE11
cnJheSBTdHJlZXQsIFN1aXRlIEw1LTAyNSwgTWFpbGJveC0yMSwgVG9yb250bywgT04sIE01VCAz
TDksIENhbmFkYS4gUmF2aS5SZXRuYWthcmFuQHNpbmFpaGVhbHRoc3lzdGVtLmNhLiYjeEQ7RGl2
aXNpb24gb2YgRW5kb2NyaW5vbG9neSwgVW5pdmVyc2l0eSBvZiBUb3JvbnRvLCBUb3JvbnRvLCBP
TiwgQ2FuYWRhLiBSYXZpLlJldG5ha2FyYW5Ac2luYWloZWFsdGhzeXN0ZW0uY2EuJiN4RDtMdW5l
bmZlbGQtVGFuZW5iYXVtIFJlc2VhcmNoIEluc3RpdHV0ZSwgTW91bnQgU2luYWkgSG9zcGl0YWws
IFRvcm9udG8sIE9OLCBDYW5hZGEuIFJhdmkuUmV0bmFrYXJhbkBzaW5haWhlYWx0aHN5c3RlbS5j
YS4mI3hEO0xlYWRlcnNoaXAgU2luYWkgQ2VudHJlIGZvciBEaWFiZXRlcywgTW91bnQgU2luYWkg
SG9zcGl0YWwsIDYwIE11cnJheSBTdHJlZXQsIFN1aXRlIEw1LTAyNSwgTWFpbGJveC0yMSwgVG9y
b250bywgT04sIE01VCAzTDksIENhbmFkYS4mI3hEO0RpdmlzaW9uIG9mIEVuZG9jcmlub2xvZ3ks
IFVuaXZlcnNpdHkgb2YgVG9yb250bywgVG9yb250bywgT04sIENhbmFkYS4mI3hEO0RlcGFydG1l
bnQgb2YgTnV0cml0aW9uYWwgU2NpZW5jZXMsIFVuaXZlcnNpdHkgb2YgVG9yb250bywgVG9yb250
bywgT04sIENhbmFkYS4mI3hEO0tlZW5hbiBSZXNlYXJjaCBDZW50cmUgZm9yIEJpb21lZGljYWwg
U2NpZW5jZSBvZiBTdCBNaWNoYWVsJmFwb3M7cyBIb3NwaXRhbCwgVG9yb250bywgT04sIENhbmFk
YS4mI3hEO0RlcGFydG1lbnQgb2YgTGFib3JhdG9yeSBNZWRpY2luZSBhbmQgUGF0aG9iaW9sb2d5
LCBVbml2ZXJzaXR5IG9mIFRvcm9udG8sIFRvcm9udG8sIE9OLCBDYW5hZGEuJiN4RDtEaXZpc2lv
biBvZiBPYnN0ZXRyaWNzIGFuZCBHeW5lY29sb2d5LCBVbml2ZXJzaXR5IG9mIFRvcm9udG8sIFRv
cm9udG8sIE9OLCBDYW5hZGEuJiN4RDtMdW5lbmZlbGQtVGFuZW5iYXVtIFJlc2VhcmNoIEluc3Rp
dHV0ZSwgTW91bnQgU2luYWkgSG9zcGl0YWwsIFRvcm9udG8sIE9OLCBDYW5hZGEuPC9hdXRoLWFk
ZHJlc3M+PHRpdGxlcz48dGl0bGU+SW1wYWN0IG9mIGRhaWx5IGluY3JlbWVudGFsIGNoYW5nZSBp
biBlbnZpcm9ubWVudGFsIHRlbXBlcmF0dXJlIG9uIGJldGEgY2VsbCBmdW5jdGlvbiBhbmQgdGhl
IHJpc2sgb2YgZ2VzdGF0aW9uYWwgZGlhYmV0ZXMgaW4gcHJlZ25hbnQgd29tZW48L3RpdGxlPjxz
ZWNvbmRhcnktdGl0bGU+RGlhYmV0b2xvZ2lhPC9zZWNvbmRhcnktdGl0bGU+PGFsdC10aXRsZT5E
aWFiZXRvbG9naWE8L2FsdC10aXRsZT48L3RpdGxlcz48ZGF0ZXM+PHllYXI+MjAxODwveWVhcj48
cHViLWRhdGVzPjxkYXRlPkF1ZyAxNTwvZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjE0
MzItMDQyOCAoRWxlY3Ryb25pYykmI3hEOzAwMTItMTg2WCAoTGlua2luZyk8L2lzYm4+PGFjY2Vz
c2lvbi1udW0+MzAxMTI2ODk8L2FjY2Vzc2lvbi1udW0+PHVybHM+PHJlbGF0ZWQtdXJscz48dXJs
Pmh0dHA6Ly93d3cubmNiaS5ubG0ubmloLmdvdi9wdWJtZWQvMzAxMTI2ODk8L3VybD48L3JlbGF0
ZWQtdXJscz48L3VybHM+PGVsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjEwLjEwMDcvczAwMTI1LTAx
OC00NzEwLTM8L2VsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjwvcmVjb3JkPjwvQ2l0ZT48L0VuZE5v
dGU+AG==
ADDIN EN.CITE.DATA [70]. Although, lncRNA and DM have attracted the attention of many scholars, but only limited research have focused on GDM. Zhang et al. investigated the relationship between lncRNA MALAT1, lncRNA p21, lncRNA H19 and GDM. They reported that the expression level of lncRNA MALAT1 was considerably higher in the GDM group as compared to the non-GDM group. Furthermore, lncRNA MALAT1 correlated with the expression of lncRNA p21 and lncRNA H19 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5aaGFuZzwvQXV0aG9yPjxZZWFyPjIwMTg8L1llYXI+PFJl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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5aaGFuZzwvQXV0aG9yPjxZZWFyPjIwMTg8L1llYXI+PFJl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ADDIN EN.CITE.DATA [71]. MALAT1 was identified as a novel serum biomarker to predict GDM. This provides a promising biomarker for future strategy to diagnose and treat GDM by regulating the expression of lncRNA MALAT1. However, in-depth studies are needed.Conclusion and Future Perspectives Increasing evidence discovered that lncRNA plays a vital role in the pathogenesis and progression of diabetes-related complicated diseases including ischemic reperfusion injury, retinopathy, cataract, atherosclerosis, cardiomyopathy, non-alcoholic steatohepatitis, gastroparesis, kidney disease and gestational diabetes mellitus. The clinical significance of MALAT1 and its molecular mechanisms in controlling these diseases are explained. This review clarifies the sophisticated researches and progresses with the possible roles of MALAT1 in different diabetic-related diseases (Figure 1). Studies had shown that the expression pattern and role of MALAT1 was similar in different types of diseases, and was up-regulated (Table 1). The expression trend of MALAT1 was consistent and the role of MALAT was even matching in the same type of cell in different researches. Additionally, MALAT1 associated number of dysregulated diseases and elevated MALAT1 levels could be a number of reasons for instance, gastric cancer, and hepatocellular carcinoma; thus, to determine the specificity of MALAT1 in the clinic, other investigations should be carried out to rule out if there are no other underlying causes. Overall, increased expression levels of MALAT1 in different diabetes-related complications, as well as MALAT1 therapeutic targeting by synthetic oligonucleotides, including miRNAs and siRNAs , have established MALAT1 as a both therapeutic target and potential biomarker. Nevertheless, there is still lack of the independent cohort study to validate, and additional miRNAs interplay and epigenetic modifications are needed, to advance the development of better-targetted therapeutic strategies. Hence, multicentre studies will be vital, which can add to the clinical utility of MALAT1 as an effective biomarker.Abbreviations:LncRNA: Long non-coding RNA; MALAT1: Metastasis-associated lung adenocarcinoma transcript 1; DM: Diabetes mellitus; MyD88: myeloid differentiation factor-88 adaptor protein; IRAK1: interleukin-1 receptor-associated kinase; TRAF6: tumor necrosis factor receptor-associated factor 6; DR: Diabetic retinopathy; PRC2: polycomb repressive complex 2; IL-6: interleukin-6; TNF-α: tumor necrosis factor-α; DC: Diabetic cataract; SP1: specificity protein 1; NLRP3: NOD-like receptor family pyrin domain containing 3; ELAVL1: embryonic lethal abnormal vision-like 1; DC: Diabetic cardiomyopathy; TNF-α: tumor necrosis factor-α; IL-1β: interleukin-1β; IL-6: interleukin-6; NO: nitric oxide; NASH: Non-alcoholic steatohepatitis; CXCL5: C-X-C motif chemokine ligand 5; α-SMA: alpha-smooth muscle actin; SM-myosin: smooth muscle myosin; SAA3: serum amyloid antigen 3; SRSF1: serine/arginine splicing factor; GDM: Gestational diabetes mellitus AcknowledgmentsWe appreciate the support from the grants by the National Natural Science Foundation of China (Grant No. 81800828).Competing InterestThe authors declare that they have no competing interest.References ADDIN EN.REFLIST 1.Guay C, Regazzi R. Circulating MicroRNAs as Novel Biomarkers for Diabetes Mellitus. Nat Rev Endocrinol. 2013; 9: 513-21.2.Whiting DR, Guariguata L, Weil C, Shaw J. IDF Diabetes Atlas: Global Estimates of the Prevalence of Diabetes for 2011 and 2030. Diabetes Res Clin Pract. 2011; 94: 311-21.3.Hanefeld M, Duetting E, Bramlage P. Cardiac Implications of Hypoglycaemia in Patients with Diabetes - A Systematic Review. Cardiovasc Diabetol. 2013; 12: 135.4.Jenkins AJ, Joglekar MV, Hardikar AA, Keech AC, O'Neal DN, Januszewski AS. Biomarkers in Diabetic Retinopathy. Rev Diabet Stud. 2015; 12: 159-95.5.Deshpande AD, Harris-Hayes M, Schootman M. Epidemiology of Diabetes and Diabetes-Related Complications. Phys Ther. 2008; 88: 1254-64.6.Rinn JL, Chang HY. Genome regulation by long noncoding RNAs. Annu Rev Biochem. 2012; 81: 145-66.7.Ravasi T, Suzuki H, Pang KC, Katayama S, Furuno M, Okunishi R, et al. Experimental validation of the regulated expression of large numbers of non-coding RNAs from the mouse genome. Genome Res. 2006; 16: 11-9.8.Liu XF, Hao JL, Xie T, Pant OP, Lu CB, Lu CW, et al. The BRAF activated non-coding RNA: A pivotal long non-coding RNA in human malignancies. Cell Prolif. 2018; 51: e12449.9.Weidle UH, Birzele F, Kollmorgen G, Ruger R. Long Non-coding RNAs and their Role in Metastasis. Cancer Genomics Proteomics. 2017; 14: 143-60.10.Su Y, Wu H, Pavlosky A, Zou LL, Deng X, Zhang ZX, et al. Regulatory non-coding RNA: new instruments in the orchestration of cell death. Cell Death Dis. 2016; 7: e2333.11.Wilusz JE, Freier SM, Spector DL. 3' end processing of a long nuclear-retained noncoding RNA yields a tRNA-like cytoplasmic RNA. Cell. 2008; 135: 919-32.12.Lei L, Chen J, Huang J, Lu J, Pei S, Ding S, et al. Functions and regulatory mechanisms of metastasis-associated lung adenocarcinoma transcript 1. J Cell Physiol. 2018 ; 234: 134-151.13.Backhouse EV, McHutchison CA, Cvoro V, Shenkin SD, Wardlaw JM. Early life risk factors for cerebrovascular disease: A systematic review and meta-analysis. Neurology. 2017; 88: 976-84.14.Lincoff AM, Nicholls SJ, Riesmeyer JS, Barter PJ, Brewer HB, Fox KAA, et al. Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease. N Engl J Med. 2017; 376: 1933-42.15.Paneni F, Luscher TF. Cardiovascular Protection in the Treatment of Type 2 Diabetes: A Review of Clinical Trial Results Across Drug Classes. Am J Cardiol. 2017; 120: S17-S27.16.Hamed SA. Brain injury with diabetes mellitus: evidence, mechanisms and treatment implications. Expert Rev Clin Pharmacol. 2017; 10: 409-28.17.Puthanveetil P, Chen S, Feng B, Gautam A, Chakrabarti S. Long non-coding RNA MALAT1 regulates hyperglycaemia induced inflammatory process in the endothelial cells. J Cell Mol Med. 2015; 19: 1418-25.18.Gao Y, Fang X, Tong Y, Liu Y, Zhang B. TLR4-mediated MyD88-dependent signaling pathway is activated by cerebral ischemia-reperfusion in cortex in mice. Biomed Pharmacother. 2009; 63: 442-50.19.Nishida A, Inatomi O, Fujimoto T, Imaeda H, Tani M, Andoh A. Interleukin-36alpha Induces Inflammatory Mediators From Human Pancreatic Myofibroblasts Via a MyD88 Dependent Pathway. Pancreas. 2017; 46: 539-48.20.Wang LQ, Zhou HJ. LncRNA MALAT1 promotes high glucose-induced inflammatory response of microglial cells via provoking MyD88/IRAK1/TRAF6 signaling. Sci Rep. 2018; 8: 8346.21.Klein BE. Overview of epidemiologic studies of diabetic retinopathy. Ophthalmic Epidemiol. 2007; 14: 179-83.22.Leasher JL, Bourne RR, Flaxman SR, Jonas JB, Keeffe J, Naidoo N, et al. Erratum. Global Estimates on the Number of People Blind or Visually Impaired by Diabetic Retinopathy: A Meta-analysis From 1990-2010. Diabetes Care 2016;39:1643-1649. Diabetes Care. 2016; 39: 2096.23.Rajavi Z, Safi S, Javadi MA, Azarmina M, Moradian S, Entezari M, et al. Diabetic Retinopathy Clinical Practice Guidelines: Customized for Iranian Population. J Ophthalmic Vis Res. 2016; 11: 394-414.24.Fu YP, Hallman DM, Gonzalez VH, Klein BE, Klein R, Hayes MG, et al. Identification of Diabetic Retinopathy Genes through a Genome-Wide Association Study among Mexican-Americans from Starr County, Texas. J Ophthalmol. 2010; 2010.25.Doria A. Genetics of diabetes complications. Curr Diab Rep. 2010; 10: 467-75.26.Yan B, Tao ZF, Li XM, Zhang H, Yao J, Jiang Q. Aberrant expression of long noncoding RNAs in early diabetic retinopathy. Invest Ophthalmol Vis Sci. 2014; 55: 941-51.27.Biswas S, Thomas AA, Chen S, Aref-Eshghi E, Feng B, Gonder J, et al. MALAT1: An Epigenetic Regulator of Inflammation in Diabetic Retinopathy. Sci Rep. 2018; 8: 6526.28.Guo F, Guo L, Li Y, Zhou Q, Li Z. MALAT1 is an oncogenic long non-coding RNA associated with tumor invasion in non-small cell lung cancer regulated by DNA methylation. Int J Clin Exp Pathol. 2015; 8: 15903-10.29. Liu JY, Yao J, Li XM, Song YC, Wang XQ, Li YJ, et al. Pathogenic role of lncRNA-MALAT1 in endothelial cell dysfunction in diabetes mellitus. Cell Death Dis. 2014; 5: e1506.30.Harding JJ, Egerton M, van Heyningen R, Harding RS. Diabetes, glaucoma, sex, and cataract: analysis of combined data from two case control studies. Br J Ophthalmol. 1993; 77: 2-6.31.Kahn HA, Leibowitz HM, Ganley JP, Kini MM, Colton T, Nickerson RS, et al. The Framingham Eye Study. II. Association of ophthalmic pathology with single variables previously measured in the Framingham Heart Study. Am J Epidemiol. 1977; 106: 33-41.32.Pollreisz A, Schmidt-Erfurth U. Diabetic cataract-pathogenesis, epidemiology and treatment. J Ophthalmol. 2010; 2010: 608751.33.Pascolini D, Mariotti SP. Global estimates of visual impairment: 2010. Br J Ophthalmol. 2012; 96: 614-8.34.Yuan L, Wang J, Xiao H, Wu W, Wang Y, Liu X. MAPK signaling pathways regulate mitochondrial-mediated apoptosis induced by isoorientin in human hepatoblastoma cancer cells. Food Chem Toxicol. 2013; 53: 62-8.35.Wu WC, Hu DN, Gao HX, Chen M, Wang D, Rosen R, et al. Subtoxic levels hydrogen peroxide-induced production of interleukin-6 by retinal pigment epithelial cells. Mol Vis. 2010; 16: 1864-73.36.Law AH, Tam AH, Lee DC, Lau AS. A role for protein phosphatase 2A in regulating p38 mitogen activated protein kinase activation and tumor necrosis factor-alpha expression during influenza virus infection. Int J Mol Sci. 2013; 14: 7327-40.37.Gong W, Zhu G, Li J, Yang X. TEMPORARY REMOVAL: "LncRNA MALAT1 promotes the apoptosis and oxidative stress of human lens epithelial cells via p38MAPK pathway in diabetic cataract". Diabetes Res Clin Pract. 2018.38.Shrikhande GV, Scali ST, da Silva CG, Damrauer SM, Csizmadia E, Putheti P, et al. O-glycosylation regulates ubiquitination and degradation of the anti-inflammatory protein A20 to accelerate atherosclerosis in diabetic ApoE-null mice. PLoS One. 2010; 5: e14240.39.Faxon DP, Fuster V, Libby P, Beckman JA, Hiatt WR, Thompson RW, et al. Atherosclerotic Vascular Disease Conference: Writing Group III: pathophysiology. Circulation. 2004; 109: 2617-25.40.Dandona P, Aljada A, Bandyopadhyay A. Inflammation: the link between insulin resistance, obesity and diabetes. Trends Immunol. 2004; 25: 4-7.41.Han Y, Qiu H, Pei X, Fan Y, Tian H, Geng J. Low-dose Sinapic Acid Abates the Pyroptosis of Macrophages by Downregulation of lncRNA-MALAT1 in Rats With Diabetic Atherosclerosis. J Cardiovasc Pharmacol. 2018; 71: 104-12.42.Falcao-Pires I, Leite-Moreira AF. Diabetic cardiomyopathy: understanding the molecular and cellular basis to progress in diagnosis and treatment. Heart Fail Rev. 2012; 17: 325-44.43.Jia G, Whaley-Connell A, Sowers JR. Diabetic cardiomyopathy: a hyperglycaemia- and insulin-resistance-induced heart disease. Diabetologia. 2018; 61: 21-8.44.Su XF, Sun L, Liu BL, Tao XJ, Li HQ, Li FF, et al. An Intensive Diabetes Screening and Treatment Program Improves Diagnosis, Treatment and Outcomes of Diabetes in Patients Admitted with Cardiac Diseases. Exp Clin Endocrinol Diabetes. 2017; 125: 151-5.45.Li G, Zou L, Xie W, Wen S, Xie Q, Gao Y, et al. The effects of NONRATT021972 lncRNA siRNA on PC12 neuronal injury mediated by P2X7 receptor after exposure to oxygen-glucose deprivation. Purinergic signalling. 2016; 12: 479-87.46.Zhang M, Gu H, Xu W, Zhou X. Down-regulation of lncRNA MALAT1 reduces cardiomyocyte apoptosis and improves left ventricular function in diabetic rats. Int J Cardiol. 2016; 203: 214-6.47.Bacci L, Barbati SA, Colussi C, Aiello A, Isidori AM, Grassi C, et al. Sildenafil normalizes MALAT1 level in diabetic cardiomyopathy. Endocrine. 2018.48.Starley BQ, Calcagno CJ, Harrison SA. Nonalcoholic fatty liver disease and hepatocellular carcinoma: a weighty connection. Hepatology. 2010; 51: 1820-32.49.Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology. 1999; 116: 1413-9.50.Rafiq N, Bai C, Fang Y, Srishord M, McCullough A, Gramlich T, et al. Long-term follow-up of patients with nonalcoholic fatty liver. Clin Gastroenterol Hepatol. 2009; 7: 234-8.51.Wong RJ, Cheung R, Ahmed A. Nonalcoholic steatohepatitis is the most rapidly growing indication for liver transplantation in patients with hepatocellular carcinoma in the U.S. Hepatology. 2014; 59: 2188-95.52.Li C, Chen J, Zhang K, Feng B, Wang R, Chen L. Progress and Prospects of Long Noncoding RNAs (lncRNAs) in Hepatocellular Carcinoma. Cell Physiol Biochem. 2015; 36: 423-34.53.Leti F, Legendre C, Still CD, Chu X, Petrick A, Gerhard GS, et al. Altered expression of MALAT1 lncRNA in nonalcoholic steatohepatitis fibrosis regulates CXCL5 in hepatic stellate cells. Transl Res. 2017; 190: 25-39 e21.54.Farrell GC, Larter CZ. Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology. 2006; 43: S99-S112.55.Gibson RS, Gibson IL, Webber CE, Atkinson SA. An improved multi-element measurement of mineral absorption in the piglet utilizing the fecal monitoring technique. Biol Trace Elem Res. 1988; 17: 139-49.56.Paradis V, Perlemuter G, Bonvoust F, Dargere D, Parfait B, Vidaud M, et al. High glucose and hyperinsulinemia stimulate connective tissue growth factor expression: a potential mechanism involved in progression to fibrosis in nonalcoholic steatohepatitis. Hepatology. 2001; 34: 738-44.57.Ali T, Hasan M, Hamadani M, Harty RF. Gastroparesis. South Med J. 2007; 100: 281-6.58.Goyal RK, Spiro HM. Gastrointestinal manifestations of diabetes mellitus. Med Clin North Am. 1971; 55: 1031-44.59.Verne GN, Sninsky CA. Diabetes and the gastrointestinal tract. Gastroenterol Clin North Am. 1998; 27: 861-74, vi-vii.60.De Block CE, De Leeuw IH, Pelckmans PA, Van Gaal LF. Current concepts in gastric motility in diabetes mellitus. Curr Diabetes Rev. 2006; 2: 113-30.61.Horvath VJ, Vittal H, Lorincz A, Chen H, Almeida-Porada G, Redelman D, et al. Reduced stem cell factor links smooth myopathy and loss of interstitial cells of cajal in murine diabetic gastroparesis. Gastroenterology. 2006; 130: 759-70.62.Bichu P, Nistala R, Khan A, Sowers JR, Whaley-Connell A. Angiotensin receptor blockers for the reduction of proteinuria in diabetic patients with overt nephropathy: results from the AMADEO study. Vasc Health Risk Manag. 2009; 5: 129-40.63.Afkarian M, Sachs MC, Kestenbaum B, Hirsch IB, Tuttle KR, Himmelfarb J, et al. Kidney disease and increased mortality risk in type 2 diabetes. J Am Soc Nephrol. 2013; 24: 302-8.64.Kanwar YS, Sun L, Xie P, Liu FY, Chen S. A glimpse of various pathogenetic mechanisms of diabetic nephropathy. Annu Rev Pathol. 2011; 6: 395-423.65.Hu M, Wang R, Li X, Fan M, Lin J, Zhen J, et al. LncRNA MALAT1 is dysregulated in diabetic nephropathy and involved in high glucose-induced podocyte injury via its interplay with beta-catenin. J Cell Mol Med. 2017; 21: 2732-47.66.Li X, Zeng L, Cao C, Lu C, Lian W, Han J, et al. Long noncoding RNA MALAT1 regulates renal tubular epithelial pyroptosis by modulated miR-23c targeting of ELAVL1 in diabetic nephropathy. Exp Cell Res. 2017; 350: 327-35.67.Wu D, Cheng YG, Huang X, Zhong MW, Liu SZ, Hu SY. Downregulation of lncRNA MALAT1 contributes to renal functional improvement after duodenal-jejunal bypass in a diabetic rat model. J Physiol Biochem. 2018; 74: 431-9.68.Metzger BE, Coustan DR. Summary and recommendations of the Fourth International Workshop-Conference on Gestational Diabetes Mellitus. The Organizing Committee. Diabetes Care. 1998; 21 Suppl 2: B161-7.69.Buchanan TA, Xiang A, Kjos SL, Watanabe R. What is gestational diabetes? Diabetes Care. 2007; 30 Suppl 2: S105-11.70.Retnakaran R, Ye C, Kramer CK, Hanley AJ, Connelly PW, Sermer M, et al. Impact of daily incremental change in environmental temperature on beta cell function and the risk of gestational diabetes in pregnant women. Diabetologia. 2018.71.Zhang Y, Wu H, Wang F, Ye M, Zhu H, Bu S. Long non-coding RNA MALAT1 expression in patients with gestational diabetes mellitus. Int J Gynaecol Obstet. 2018; 140: 164-9. Figure Legend Figure 1. Various regulatory mechanisms of MALAT1 in different diabetes-related complications.(a). Hyperglycaemia-induced MALAT1 trigger an inflammatory response in microglial cells via activation of MyD88 signalling leading to ischemic reperfusion injury.(b). MALAT1 recruits PRC2 to bind anti-inflammatory gene promoter which suppresses its transcription and subsequently increases inflammatory response leading to retinopathy.(c). Hyperglycaemia induces Sp1 protein binding to the MALAT1 promoter gene increasing MALAT1 expression, increased MALAT1 activates p38MAPK pathway causing apoptosis and oxidative stress leading to cataract formation.(d). MALAT1 inhibits miR-23 which in turn increases ELAVL1 and NLRP3 leading to atherosclerosis.(e). Hyperglycaemia promotes MALAT1 levels which trigger inflammatory cytokines TNF-α, IL-1β and IL-6 leading to inflammation and cardiomyopathy. (f). MALAT1 promotes cxcl5 chemokine via cxcl5 gene transcript which triggers inflammation, fibrosis and NASH.(g). MALAT1 decreases α-SMA, SM myosin heavy chain diminishes contractility leading to gastroparesis. (h). MALAT1 antagonized the effect of miR-23 on its target ELAVL1, NLRP3 promoting pyroptosis and diabetic nephropathy.Table 1: MALAT1 Influences in Diabetes-associated ComplicationsDiseases Expression Relatedmolecules Model RoleReferences Cerebrovascular Disease Up-regulatedMyD88, IRAK1 TRAF6In vitro and in vivoInflammation 20Diabetic RetinopathyUp-regulatedPRC2, IL-6 and TNF-αIn vivo and vitroProliferation 27,26Diabetic Cataract Up-regulatedp38,SP1In vivo and vitroApoptosis 37AtherosclerosisUp-regulatedNLRP3, ELAVL1, miR-23cIn vivoApoptosis 41Diabetic CardiomyopathyUp-regulatedTNF-α, IL-1β IL-6, NOIn vitro and in vivoApoptosis 45,46Non-alcoholic SteatohepatitisUp-regulatedCXCL5In vivoInflammation 53Diabetic GastroparesisUp-regulatedα-SMA, SM- myosinIn vivo- 61,72Diabetic Kidney DiseaseUp-regulatedSAA3, IL-6, ELAVL1, NLRP3, Caspase-1, SRSF1In vitro and in vivo Inflammation, pyroptosis 65-67Gestational DiabetesUp-regulated-In vivo- 71Note: MyD88: myeloid differentiation factor-88 adaptor protein; IRAK1: interleukin-1 receptor-associated kinase; TRAF6: tumor necrosis factor receptor-associated factor 6; PRC2: polycomb repressive complex 2; IL-6: interleukin-6; TNF-α: tumor necrosis factor-α; SP1: specificity protein 1; NLRP3: NOD-like receptor family, pyrin domain containing 3; ELAVL1: embryonic lethal, abnormal vision-like; IL-1β: interleukin-1β; IL-6: interleukin-6; NO: nitric oxide; CXCL5: C-X-C motif chemokine ligand 5; α-SMA: alpha smooth muscle actin; SM myosin: smooth muscle myosin; SAA3: serum amyloid antigen 3; SRSF1: serine/arginine splicing factor. ................
................
In order to avoid copyright disputes, this page is only a partial summary.
To fulfill the demand for quickly locating and searching documents.
It is intelligent file search solution for home and business.
Related searches
- international journal of management education
- international journal of economic papers
- international journal of financial management
- nature international journal of science
- international journal of biological
- international journal of biological sciences
- international journal of experimental biology
- international journal of philosophy
- international journal of mathematics
- international journal of biological science
- international journal of cell biology
- international journal of medical sciences