Downregulation of microRNA-195 promotes angiogenesis induced by cerebral infarction via targeting VEGFA

Angiogenesis, the formation of new blood vessels from preexisting endothelium, is a process that involves a series of interassociated and mutually interactive pathophysiological processes. It is accepted that microRNAs (miRNAs) regulate endothelial cell behavior, including their involvement in angiogenesis. However, it remains unclear whether miRNAs are involved in the regulation of angiogenesis following cerebral ischemia. Therefore, the present study aimed to investigate the role of miRNAs in angiogenesis and the underlying mechanism following cerebral ischemia. Expression profiles of miRNAs in rat brain samples following middle cerebral artery occlusion (MCAO) were investigated using a miRNA microarray. The expression of candidate miRNA, miR-195 was further validated using reverse transcription-quantitative polymerase chain reaction. Then, the effects of miR-195 on cell migration and tube formation of human umbilical vein vascular endothelial cells (HUVECs) were investigated following miR-195 silencing, and overexpression. The specific target genes of miR-195 were predicted using microRNA prediction bioinformatics software (http://www.microrna.org/microrna/home.do), and then confirmed using a dual-luciferase reporter assay and rescue experiment. It was demonstrated that miR-195 was significantly downregulated in the brains of rats following MCAO and in hypoxia-induced HUVECs. Furthermore, it was revealed that miR-195 overexpression inhibited the invasion ability and tube formation of HUVECs in vitro, while miR-195 silencing enhanced these functions. In addition, vascular endothelial growth factor A (VEGFA) was identified as a direct target of miR-195 and was negatively correlated with miR-195 expression. In addition, the rescue experiment revealed that overexpression of VEGFA reversed the inhibitory effects of miR-195 overexpression on the invasion ability and tube formation of HUVECs. The present study has provided a novel insight into the promoting roles of miR-195 downregulation on angiogenesis following cerebral infarction and suggests that the miR-195/VEGFA signaling pathway is a putative therapeutic target in cerebral ischemia.