MicroRNA-433 Inhibits the Proliferation and Migration of HUVECs and Neurons by Targeting Hypoxia-Inducible Factor 1 Alpha.

Emerging evidence has demonstrated an important role of microRNAs (miRNAs) in the pathogenesis of cerebral infarction. In the present study, a down-regulation of microRNA-433 (miR-433) is identified in hypoxia-induced human umbilical vein vascular endothelial cells (HUVECs) as well as in rat neurons, and is found to be negatively regulated cell proliferation and migration. Moreover, the expression of miR-433 is inversely correlated with the expression of hypoxia-inducible factor 1 alpha (HIF-1α), which has been shown to play critical role in responding to hypoxia conditions. Overexpression or knockdown of miR-433 responsively alters both mRNA and protein levels of HIF-1α and its downstream genes, vascular endothelial growth factor, Glut-1, and Angpt2. In a luciferase reporter system, miR-433 down-regulates the luciferase activity of HIF-1α 3'-UTR, and these effects are abolished by a mutation in the putative miR-433-binding site. Further investigation confirms that knockdown of HIF-1α blocked the stimulatory effect of anti-miR-433, while overexpression of HIF-1α reversed the inhibitory effects of pre-miR-433 on proliferation and migration of HUVEC and neurons. Taken together, our findings indicate that miR-433 plays an important role in response to hypoxia, inhibiting HUVEC and neuron proliferation and migration by down-regulating HIF-1α.