lncRNA-MIAT regulates microvascular dysfunction by functioning as a competing endogenous RNA

Circ Res. 2015 Mar 27;116(7):1143-56. doi: 10.1161/CIRCRESAHA.116.305510. Epub 2015 Jan 13.

Abstract

Rationale: 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.

Methods and 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.

Keywords: angiogenesis inhibitors; epigenomics; long noncoding RNA; vascular endothelial growth factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Binding, Competitive
  • Cells, Cultured
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetic Retinopathy / genetics*
  • Diabetic Retinopathy / metabolism
  • Diabetic Retinopathy / physiopathology
  • Electroretinography
  • Endothelial Cells / metabolism*
  • Eye Proteins / biosynthesis
  • Eye Proteins / genetics
  • Feedback, Physiological
  • Gene Expression Profiling
  • Glucose / pharmacology
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Macaca mulatta
  • Mice
  • Mice, Mutant Strains
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / metabolism
  • RNA Interference
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / biosynthesis
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Retina / metabolism*
  • Retina / pathology
  • Retinal Neovascularization / genetics*
  • Vascular Endothelial Growth Factor A / physiology

Substances

  • Eye Proteins
  • MIRN150 microRNA, human
  • MIRN150 microRNA, rat
  • Miat long non-coding RNA
  • MicroRNAs
  • RNA, Long Noncoding
  • Vascular Endothelial Growth Factor A
  • Glucose