Circular RNA circ_0010283 regulates the viability and migration of oxidized low-density lipoprotein-induced vascular smooth muscle cells via an miR-370-3p/HMGB1 axis in atherosclerosis

Abstract

Atherosclerosis is a disease during which the inside of an artery narrows due to the accumulation of plaque, and vascular smooth muscle cells (VSMCs) are involved in the progression of atherosclerosis. Circular RNAs (circRNAs) have been reported to be involved in the progression of atherosclerosis. However, the role of circ_0010283 in atherosclerosis progression remains unclear. The present study aimed to investigate the functions and the mechanism of circ_0010283 in oxidized low-density lipoprotein (ox-LDL)-induced VSMCs and to identify new potential biomarkers for the treatment of atherosclerosis. Cell viability and migration were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Transwell assays. The relationship between microRNA (miR)-370-3p and circ_0010283 or high mobility group box 1 (HMGB1) was predicated by online software and confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay. The results of the present study demonstrated that the expression levels of circ_0010283 and HMGB1 were significantly upregulated in ox-LDL-induced VSMCs compared with those in VSMCs without ox-LDL induction, whereas the expression of miR-370-3p was downregulated. Knockdown of circ_0010283 suppressed VSMC viability and migration, as well as the expression of viability-associated proteins cyclin D1 and proliferating cell nuclear antigen, and migration-associated proteins matrix metalloproteinase 2 (MMP2) and MMP9 in ox-LDL-induced VSMCs compared with untreated VSMCs. In addition, miR-370-3p was demonstrated to be a target of circ_0010283 and to target HMGB1; thus, circ_0010283 regulated HMGB1 expression via miR-370-3p. Further experiments indicated that inhibition of miR-370-3p reversed the circ_0010283 silencing-mediated inhibitory effects on VMSC viability and migration. Additionally, the miR-370-3p-mediated suppressive effects on cell viability and migration were rescued by overexpression of HMGB1. In conclusion, circ_0010283 mediated cell viability and migration via a miR-370-3p/HMGB1 axis in ox-LDL-induced VSMCs.