Circular RNA circ_0002984 Promotes Cell Proliferation and Migration by Regulating miR-181b-5p/Vascular Endothelial Growth Factor Axis and PI3K-AKT Signaling Pathway in Oxidized Low-Density Lipoprotein–Treated Vascular Smooth Muscle Cells

Abstract: RNAs (circRNAs) play critical roles in many diseases, including atherosclerosis (AS). However, the role and underlying mechanism of circ_0002984 in AS remain unclear. Vascular smooth muscle cells (VSMCs) treated with oxidized low-density lipoprotein (ox-LDL) were used as a AS cell model. Quantitative real-time polymerase chain reaction was conducted to detect the expression of circ_0002984, miR-181b-5p and vascular endothelial growth factor A (VEGFA). Cell proliferation was evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide assay and 5-ethynyl-2′-deoxyuridine assays. Cell migration was assessed using wound healing assay and transwell assay. All protein levels were analyzed by western blot assay. The interaction between miR-181b-5p and circ_0002984 or VEGFA was confirmed by dual-luciferase reporter, RNA Immunoprecipitation, and RNA pull-down assays. Circ_0002984 and VEGFA were overexpressed, and miR-181b-5p was downregulated in serum of AS patients and ox-LDL–stimulated VSMCs. Circ_0002984 silencing inhibited ox-LDL–induced proliferation and migration in VSMCs. MiR-181b-5p was a target of circ_0002984, and miR-181b-5p inhibition counteracted the suppressing effects of circ_0002984 downregulation on proliferation and migration in ox-LDL–stimulated VSMCs. Additionally, VEGFA was a downstream target of miR-181b-5p and VEGFA upregulation abolished the suppressive influence of miR-181b-5p on proliferation and migration in ox-LDL–exp...
Source: Journal of Cardiovascular Pharmacology - Category: Cardiology Tags: Original Article Source Type: research