MiR-147b influences vascular smooth muscle cell proliferation and migration via targeting YY1 and modulating Wnt/β-catenin activities

Abstract

Cardiovascular disease is the leading cause of death worldwide. Dysregulation of microRNAs (miRNAs) has been found to be associated with cardiovascular diseases such as atherosclerosis. In the present study, we examined the role of miR-147b in the proliferation and migration of vascular smooth muscle cells (VSMCs). Quantitative real-time PCR was performed to determine the expression levels of miR-147b and Yin Yang 1 (YY1) mRNA. CCK-8, transwell migration and wound healing assays were used to determine cell proliferation and migration of VSMCs, respectively. Luciferase reporter assay confirmed the downstream target of miR-147b. The protein level of YY1 was measured by western blot analysis. Platelet-derived growth factor-bb (PDGF-bb) treatment promoted cell proliferation and increased miR-147b expression in VSMCs. Overexpression of miR-147b enhanced cell proliferation and migration of VSMCs, while knock-down of miR-147b suppressed cell proliferation and migration of VSMCs or PDGF-bb-treated VSMCs. Further, bioinformatics prediction and luciferase reporter assay showed that YY1 was a downstream target of miR-147b, and miR-147b negatively regulated the mRNA and protein expression of YY1 in VSMCs. Overexpression of YY1 inhibited cell proliferation and migration of VSMCs and attenuated the effects of miR-147b overexpression on cell proliferation and migration. In addition, overexpression of miR-147b increased the Wnt/β-catenin signaling activities in VSMCs. In conclusion, our results suggest that miR-147b plays important roles in the control of cell proliferation and migration of VSMCs possibly via targeting YY1.