The Role Of MicroRNA-146a In Regulating Proliferation And Apoptosis Of Vascular Smooth Muscle Cell And Its Mechanisms

It is putative that the development of proliferative caridovascular diseases is an exquisitelyorchestrated process that involves cascade responses of inflammation and immunity, subsequentactivation, proliferation, migration of vascular smooth muscle cell (VSMC) as well asaccelerated synthesis of extracellular matrix (ECM) components and eventual formation ofneointimal lesion. MicroRNA-146a (miR-146a), which plays a crucial role in modulation ofinflammational and immune reaction, regulates expression of nuclear factor-κB (NF-κB) tomaintain internal environment homeostasis in a negative feedback pattern in tumor andautoimmune diseases. Recently, increased expression of miR-146a was confirmed in vascularwall after angioplasty, indicting miR-146a may participate in the development of atherosclerosisand postangioplasty restenosis.In our present study, we employed RNA interference technology to synthesize miR-146ainhibitor and transfect it to VSMC. We verified that miR-146a inhibitor can downregulatemiR-146a expression in dose-dependent manner. After knockdown of miR-146a, VSMCexhibited low proliferative and migratory properties, high apoptotic aspects, which accompaniedwith upregulation of NF-κBp65and proliferating cell nuclear antigen (PCNA) protein level,downregulation of Bax protein level.In summary, we revealed that the noncoding small miRNA miR-146a is a novel regulator ofVSMC proliferation, migration and apoptosis. The proproliferative effect of miR-146a in VSMCwas mediated by induction of NF-κB avtivation, while antiapoptotic effect of miR-146a wasmediated by repression of Bax expression. Our data suggested that miR-146a may participate inthe pathological process of proliferative caridovascular diseases.