MicroRNA-370 suppresses the retinal capillary endothelial cell growth by targeting KDR gene.

Abstract

Ocular neovascularization (NV) is the one of the major causes of blindness in many ocular diseases. Currently, the administration of anti-VEGF agents has been widely accepted for the clinical management of these devastating diseases. However, the short effective duration and the non-responsive rate due to the protein nature of the anti-VEGF antibodies warrants further investigations to explore alternative angiogenic suppressants. Evidence suggested that microRNA-370 could inhibit the formation of vessels. However, the exact mechanism has not yet been clarified. To investigate the regulatory role of microRNA-370 in the growth and apoptosis of retinal capillary endothelial cells and association between microRNA-370 and kinase insert domain-containing receptor (KDR) gene. The effects of miRNA-370 on cell cycle and apoptosis, as well as the expression of cycle- and apoptosis-related genes, were determined using MTT, TUNEL assay, qRT-PCR, and Western blot. The direct target of miRNA-370 was confirmed using 3' untranslated region (UTR) luciferase reporter assay. The miRNA-370 induced growth inhibition and apoptosis of retinal capillary endothelial cell while the inhibition of miRNA-370 reversed these effects. miRNA-370 upregulated the expression of CyclinD1, p21, p27, FasL, and Bim. Furthermore, miR-370 directly reduced the expression of KDR by targeting its 3'untranslated region. MicroRNA-370 inhibits the expression of KDR gene resulting in retinal capillary endothelial cell growth inhibition and apoptosis, which could be of value in the treatment of retinal neovascularization (Tab. 1, Fig. 5, Ref. 27).