Downregulation of miR‑142‑5p inhibits human aortic smooth muscle cell proliferation and migration by targeting MKL2.

Abstract

The increased proliferation and migration of vascular smooth muscle cells (VSMCs) are critical in the progression of atherosclerosis (AS). Platelet-derived growth factor type BB (PDGF-BB) may induce VSMC proliferation and migration. miR-142-5p plays a critical role in various biological processes, including tumorigenesis, angiogenesis and inflammation. However, whether miR-142-5p is involved in regulating the pathological process of arteriosclerosis remains to be elucidated. Therefore, in this study, the role of miR-142-5p in PDGF-BB-induced human aortic smooth muscle cell (HSAMC) proliferation and migration was investigated. The results revealed that the expression level of miR-142-5p was enhanced in the serum of patients with AS, while that of its target gene, myocardin-like protein 2 (MKL2) was decreased, compared with that in healthy volunteers. Moreover, there was a negative correlation between miR-142-5p and MKL2 expression in the serum of patients with AS. Furthermore, the downregulation of miR-142-5p inhibited PDGF-BB-induced HASMC proliferation and migration; however, the inhibition of HASMC proliferation and migration was reversed by co-transfection with small interfering RNA (siRNA) against MKL2 (siRNA-MKL2). In addition, transfection with miR-142-5p inhibitor significantly increased the expression levels of MKL2, and decreased those of matrix metalloproteinase (MMP)2 and 9, and these effects were reversed by transfection with siRNA-MKL2. Finally, MKL2 was proven to be a target of miR-142-5p. On the whole, the findings of the present study demonstrate that the downregulation of miR-142-5p inhibits human aortic smooth muscle cell (HSAMC) proliferation and migration possibly by targeting MKL2. Hence, miR-142-5p may prove to be a novel therapeutic target in the treatment of AS.