Identification of microRNA-365 as a negative regulator of endothelial cell proliferation

Abstract

Recent studies have shown that human microRNA miR-365 has significant inhibitory effects on proliferation of transformed cancer cells and vascular smooth muscle cells. However, the effects of miR-365 on proliferation and migration of vascular endothelial cells remain unknown. Using human umbilical vein endothelial cells and in vitro assays, we demonstrated that miR-365 was a suppressor of endothelial cell proliferation, whereas cell migration was not affected by miR-365. We also identified that the expression level of the serine/threonine protein kinase serum- and glucocorticoid-regulated kinase-1 (SGK-1) was regulated by miR-365. The cytostatic effect of miR-365 was mimicked by the specific SGK-1 inhibitor GSK 650394. We further demonstrated that microvesicles isolated from plasma of patients with intracerebral hemorrhage, in which the level of miR-365 was elevated, decreased the expression level of SGK-1, and this effect was abolished in cells pretreated with miR-365 antagomir. However, we did not observe a significant effect of the microvesicles on cell proliferation. It is suggested that miR-365 may have important roles in vascular physiology and/or pathophysiology by modulating endothelial cell proliferation.