MicroRNA-761 inhibits Angiotensin II-induced vascular smooth muscle cell proliferation and migration by targeting mammalian target of rapamycin

Abstract

Aberrant vascular smooth muscle cell (VSMC) proliferation and migration are a major pathological phenomenon in vascular disease characterized by intimal thickening. The important role of the mammalian target of rapamycin (mTOR) signaling in VSMC proliferation has been previously reported. Consequently, down-regulation of mTOR pathway may be an effective way of controlling excessive VSMC proliferation. Since microRNAs (miRNA) are newly emerging regulators of virtually all the biological processes including cellular proliferation, miRNAs targeting mTOR pathway may be utilized to suppress aberrant VSMC proliferation during pathologic conditions. Thus, in the present study, we screened miRNAs targeting mTOR, and we identified miR-761 as a new mTOR targeting miRNA. Luciferase assay using luciferase vector containing 3'UTR of mTOR indicated that miR-761 directly targets mTOR mRNA leading to suppression of mTOR protein expression. Our data also indicate that miR-761 expression decreases during angiotensin II (AngII)-induced proliferation of VSMCs, and exogenous miR-761 delivery effectively inhibit the AngII-induced VSMC proliferation. Additionally, the results of migration tests demonstrate that down-regulation of mTOR using exogenous miR-761 suppresses AngII-induced migration of VSMCs as well. Taken together, the present study provided evidence that miR-761 can be a potent anti-proliferative agent for vascular diseases such as atherosclerosis and restenosis, and warrants further studies to validate the effectiveness of miR-761 in vivo.