Effect of microRNA-30e on the behavior of vascular smooth muscle cells via targeting ubiquitin-conjugating enzyme E2I

Abstract

Background: Many microRNAs (miRNAs) have recently been shown to demonstrate critical roles in differentiation, proliferation and migration of vascular smooth muscle cells (VSMCs). Methods and Results: In this study, a certain amount of miRNA expression in VSMCs was evaluated by real-time polymerase chain reaction, and it was found that microRNA-30e (miR-30e) was expressed more strongly than other common vascular well-expressed miRNAs in vitro. Subsequently, both a gain and loss of function study was performed in vitro and in vivo. It was found that miR-30e in VSMCs was strongly downregulated concomitantly with stimulation, and miR-30e inhibited VSMCs proliferation and migration both in vitro and in vivo. Furthermore, ubiquitin-conjugating enzyme E2I (Ube2i) was identified as the target gene of endogenous miR-30e by luciferase reporter assay, and it was confirmed that overexpression of miR-30e significantly reduced Ube2i and inhibited the phenotypic switch of VSMCs. Knockdown of Ube2i had an influence over the proliferation and migration of cultured VSMCs, as same as the miR-30e mimic did. Overexpression of miR-30e induced the apoptosis of VSMCs and deregulated the protein expression of IkBα, which is crucial for the NFκB signal pathway. Conclusions: The results of this study indicated that miR-30e in VSMCs exerted an anti-atherosclerosis effect via inhibiting proliferation and migration, and promoting apoptosis of VSMCs. More specifically, it was demonstrated that miR-30e exhibited these effects on VSMCs partially through targeting Ube2i and downregulating the IκBα/NFκB signaling pathway.