MicroRNA-199a-3p Exhibits Beneficial Effects in Asymptomatic Atherosclerosis by Inhibiting Vascular Smooth Muscle Cell Proliferation and Migration

Abstract

Atherosclerosis (AS) is a serious healthy burden worldwide, it occurs accompany with the disfunction of vascular smooth muscle cells (VSMCs). MicroRNAs play pivotal role in the pathogenesis of various diseases. This study aimed to investigate the expression and clinical value of miR-199a-3p in patients with asymptomatic AS, and further explore its regulatory role on VSMCs biological function. Quantitative real-time PCR was used to estimate the expression of miR-199a-3p. Correlation of miR-199a-3p with carotid intima-media thickness (CIMT) and C-reactive protein (CRP) was evaluated by Pearson correlation coefficient. A receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of miR-199a-3p. Effects of miR-199a-3p on cell proliferation and migration in VSMCs were analyzed using cell-counting method and Transwell assay. Luciferase reporter assay was performed for the target gene analysis. Serum expression of miR-199a-3p was decreased in asymptomatic AS patients compared with the healthy controls. The negative correlations of miR-199a-3p with CIMT and CRP were obtained. The decreased miR-199a-3p was proved to have diagnostic accuracy with an area under the ROC curve (AUC) of 0.912, and was an independent predictor for the occurrence of asymptomatic AS. In VSMCs, overexpression of miR-199a-3p led to inhibited cell proliferation and migration, while the knockdown of miR-199a-3p resulted in the opposite results. SP1 was proved to be the target gene of miR-199a-3p. Taken together, downregulated expression of miR-199a-3p is a candidate diagnostic biomarker in the patients with asymptomatic AS. Overexpression of miR-199a-3p exists suppressive effects on VSMC proliferation and migration, indicating that miR-199a-3p may be a potential therapeutic target for AS treatment.