LncRNA-MIAT Regulates Microvascular Dysfunction by Functioning as a Competing Endogenous RNA
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. LncRNAs have emerged as critical regulators of these biological processes. However, the role of lncRNA in diabetes-induced microvascular dysfunction is largely unknown.
Objective: To elucidate whether lncRNA-MIAT is involved in diabetes-induced microvascular dysfunction.
Methods and Results: Using quantitative PCR, 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-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 ceRNA, and formed a feedback loop with VEGF 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.
- competing endogenous RNA
- vascular growth factor
- non-coding RNA
- microvascular dysfunction
- Received October 25, 2014.
- Revision received January 8, 2015.
- Accepted January 13, 2015.