title: lncRNA-MIAT regulates microvascular dysfunction by functioning as a competing endogenous RNA.
abstract: BACKGROUND
  Pathological angiogenesis is a critical component of diseases, such as ocular disorders, cancers, and atherosclerosis. It is usually caused by the abnormal activity of biological processes, such as cell proliferation, cell motility, immune, or inflammation response. Long noncoding RNAs (lncRNAs) have emerged as critical regulators of these biological processes. However, the role of lncRNA in diabetes mellitus-induced microvascular dysfunction is largely unknown.
  
  
  OBJECTIVE
  To elucidate whether lncRNA-myocardial infarction-associated transcript (MIAT) is involved in diabetes mellitus-induced microvascular dysfunction.
  
  
  RESULTS
  Using quantitative polymerase chain reaction, we demonstrated increased expression of lncRNA-MIAT in diabetic retinas and endothelial cells cultured in high glucose medium. Visual electrophysiology examination, TUNEL staining, retinal trypsin digestion, vascular permeability assay, and in vitro studies revealed that MIAT knockdown obviously ameliorated diabetes mellitus-induced retinal microvascular dysfunction in vivo, and inhibited endothelial cell proliferation, migration, and tube formation in vitro. Bioinformatics analysis, luciferase assay, RNA immunoprecipitation, and in vitro studies revealed that MIAT functioned as a competing endogenous RNA, and formed a feedback loop with vascular endothelial growth factor and miR-150-5p to regulate endothelial cell function.
  
  
  CONCLUSIONS
  This study highlights the involvement of lncRNA-MIAT in pathological angiogenesis and facilitates the development of lncRNA-directed diagnostics and therapeutics against neovascular diseases.
authors.affiliation: From the Department of Central Laboratory, Eye Hospital (B.Y., J.-Y.L., J.Y., X.-M.L., X.-Q.W., Y.-J.L., Z.-F.T., Y.-C.S., Q.J.), Department of Ophthalmology, The Fourth School of Clinical Medicine (B.Y., J.Y., Q.J.), and Department of Pathophysiology, School of Basic Medical Sciences (Q.C.), Nanjing Medical University, Nanjing, China. yanbiao1982@hotmail.com jqin710@vip.sina.com.cn.
authors.forename: Biao
authors.initials: B
authors.lastname: Yan
authors.affiliation: From the Department of Central Laboratory, Eye Hospital (B.Y., J.-Y.L., J.Y., X.-M.L., X.-Q.W., Y.-J.L., Z.-F.T., Y.-C.S., Q.J.), Department of Ophthalmology, The Fourth School of Clinical Medicine (B.Y., J.Y., Q.J.), and Department of Pathophysiology, School of Basic Medical Sciences (Q.C.), Nanjing Medical University, Nanjing, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Yao
authors.affiliation: From the Department of Central Laboratory, Eye Hospital (B.Y., J.-Y.L., J.Y., X.-M.L., X.-Q.W., Y.-J.L., Z.-F.T., Y.-C.S., Q.J.), Department of Ophthalmology, The Fourth School of Clinical Medicine (B.Y., J.Y., Q.J.), and Department of Pathophysiology, School of Basic Medical Sciences (Q.C.), Nanjing Medical University, Nanjing, China.
authors.forename: Jing-Yu
authors.initials: JY
authors.lastname: Liu
authors.affiliation: From the Department of Central Laboratory, Eye Hospital (B.Y., J.-Y.L., J.Y., X.-M.L., X.-Q.W., Y.-J.L., Z.-F.T., Y.-C.S., Q.J.), Department of Ophthalmology, The Fourth School of Clinical Medicine (B.Y., J.Y., Q.J.), and Department of Pathophysiology, School of Basic Medical Sciences (Q.C.), Nanjing Medical University, Nanjing, China.
authors.forename: Xiu-Miao
authors.initials: XM
authors.lastname: Li
authors.affiliation: From the Department of Central Laboratory, Eye Hospital (B.Y., J.-Y.L., J.Y., X.-M.L., X.-Q.W., Y.-J.L., Z.-F.T., Y.-C.S., Q.J.), Department of Ophthalmology, The Fourth School of Clinical Medicine (B.Y., J.Y., Q.J.), and Department of Pathophysiology, School of Basic Medical Sciences (Q.C.), Nanjing Medical University, Nanjing, China.
authors.forename: Xiao-Qun
authors.initials: XQ
authors.lastname: Wang
authors.affiliation: From the Department of Central Laboratory, Eye Hospital (B.Y., J.-Y.L., J.Y., X.-M.L., X.-Q.W., Y.-J.L., Z.-F.T., Y.-C.S., Q.J.), Department of Ophthalmology, The Fourth School of Clinical Medicine (B.Y., J.Y., Q.J.), and Department of Pathophysiology, School of Basic Medical Sciences (Q.C.), Nanjing Medical University, Nanjing, China.
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Li
authors.affiliation: From the Department of Central Laboratory, Eye Hospital (B.Y., J.-Y.L., J.Y., X.-M.L., X.-Q.W., Y.-J.L., Z.-F.T., Y.-C.S., Q.J.), Department of Ophthalmology, The Fourth School of Clinical Medicine (B.Y., J.Y., Q.J.), and Department of Pathophysiology, School of Basic Medical Sciences (Q.C.), Nanjing Medical University, Nanjing, China.
authors.forename: Zhi-Fu
authors.initials: ZF
authors.lastname: Tao
authors.affiliation: From the Department of Central Laboratory, Eye Hospital (B.Y., J.-Y.L., J.Y., X.-M.L., X.-Q.W., Y.-J.L., Z.-F.T., Y.-C.S., Q.J.), Department of Ophthalmology, The Fourth School of Clinical Medicine (B.Y., J.Y., Q.J.), and Department of Pathophysiology, School of Basic Medical Sciences (Q.C.), Nanjing Medical University, Nanjing, China.
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Song
authors.affiliation: From the Department of Central Laboratory, Eye Hospital (B.Y., J.-Y.L., J.Y., X.-M.L., X.-Q.W., Y.-J.L., Z.-F.T., Y.-C.S., Q.J.), Department of Ophthalmology, The Fourth School of Clinical Medicine (B.Y., J.Y., Q.J.), and Department of Pathophysiology, School of Basic Medical Sciences (Q.C.), Nanjing Medical University, Nanjing, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.affiliation: From the Department of Central Laboratory, Eye Hospital (B.Y., J.-Y.L., J.Y., X.-M.L., X.-Q.W., Y.-J.L., Z.-F.T., Y.-C.S., Q.J.), Department of Ophthalmology, The Fourth School of Clinical Medicine (B.Y., J.Y., Q.J.), and Department of Pathophysiology, School of Basic Medical Sciences (Q.C.), Nanjing Medical University, Nanjing, China. yanbiao1982@hotmail.com jqin710@vip.sina.com.cn.
authors.forename: Qin
authors.initials: Q
authors.lastname: Jiang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001667:Binding, Competitive; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D004596:Electroretinography; D042783:Endothelial Cells / Q000378:metabolism*; D005136:Eye Proteins / Q000096:biosynthesis / Q000235:genetics; D025461:Feedback, Physiological; D020869:Gene Expression Profiling; D005947:Glucose / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008253:Macaca mulatta; D051379:Mice; D008817:Mice, Mutant Strains; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000378:metabolism; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D015861:Retinal Neovascularization / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
chemical_list: D005136:Eye Proteins; D005947:Glucose; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D042461:Vascular Endothelial Growth Factor A; C533097:MIR150, human; C551974:MIRN150 microRNA, rat; C517383:Miat long non-coding RNA
keywords: angiogenesis inhibitors; epigenomics; long noncoding RNA; vascular endothelial growth factor