Department of Vascular Surgery, Xiamen Cardiovascular Hospital of Xiamen University, Xiamen, China.
Department of Stomatology, Zhongshan Hospital, Xiamen University, Xiamen, China.
Shock. 2023 Aug 1;60(2):181-189. doi: 10.1097/SHK.0000000000002163. Epub 2023 Jun 10.
Background: Circular RNAs (circRNAs) have been shown to mediate atherosclerosis (AS) process by regulating vascular smooth muscle cells (VSMCs) function. However, whether circ_0091822 mediates VSMCs function to regulate AS process is unclear. Methods: Oxidized low-density lipoprotein (ox-LDL) was used to treat VSMCs for constructing AS cell models. Vascular smooth muscle cells proliferation, invasion, and migration were examined by cell counting kit 8 assay, EdU assay, transwell assay, and wound healing assay. Protein expression was tested by western blot analysis. The expression of circ_0091822, microRNA (miR)-339-5p, and blocking of proliferation 1 (BOP1) was determined using quantitative real-time PCR. RNA interaction was examined using dual-luciferase reporter assay and RIP assay. Results: Ox-LDL treatment enhanced VSMCs proliferation, invasion, and migration. Circ_0091822 was overexpressed in the serum of AS patients and ox-LDL-induced VSMCs. Circ_0091822 knockdown inhibited ox-LDL-induced VSMCs proliferation, invasion, and migration. Circ_0091822 sponged miR-339-5p, and miR-339-5p inhibitor reversed the function of circ_0091822 knockdown. MiR-339-5p targeted BOP1, and BOP1 also reversed the repressing effect of miR-339-5p on ox-LDL-induced VSMCs functions. Circ_0091822/miR-339-5p/BOP1 axis promoted the activity of Wnt/β-catenin pathway. Conclusions: Circ_0091822 might be a therapeutic target for AS, which facilitated ox-LDL-induced VSMCs proliferation, invasion, and migration through modulating miR-339-5p/BOP1/Wnt/β-catenin pathway.
环状 RNA（circRNAs）已被证明通过调节血管平滑肌细胞（VSMCs）功能来介导动脉粥样硬化（AS）进程。然而，circ_0091822 是否通过调节 VSMCs 功能来调节 AS 进程尚不清楚。方法：用氧化型低密度脂蛋白（ox-LDL）处理 VSMCs 构建 AS 细胞模型。通过细胞计数试剂盒 8 检测、EdU 检测、transwell 检测和划痕愈合实验检测 VSMCs 的增殖、侵袭和迁移。通过 Western blot 分析检测蛋白表达。采用实时定量 PCR 检测 circ_0091822、微小 RNA（miR）-339-5p 和增殖抑制因子 1（BOP1）的表达。采用双荧光素酶报告基因检测和 RIP 实验检测 RNA 相互作用。结果：ox-LDL 处理增强了 VSMCs 的增殖、侵袭和迁移。AS 患者血清和 ox-LDL 诱导的 VSMCs 中 circ_0091822 表达上调。circ_0091822 敲低抑制了 ox-LDL 诱导的 VSMCs 增殖、侵袭和迁移。circ_0091822 可吸附 miR-339-5p，miR-339-5p 抑制剂逆转了 circ_0091822 敲低的功能。miR-339-5p 靶向 BOP1，BOP1 也逆转了 miR-339-5p 对 ox-LDL 诱导的 VSMCs 功能的抑制作用。circ_0091822/miR-339-5p/BOP1 轴促进了 Wnt/β-catenin 通路的活性。结论：circ_0091822 可能是 AS 的一个治疗靶点，它通过调节 miR-339-5p/BOP1/Wnt/β-catenin 通路促进 ox-LDL 诱导的 VSMCs 增殖、侵袭和迁移。
