Department of Ultrasonic Imaging, Affiliated Renhe Hospital of China Three Gorges University, No.410, Yiling Avenue, Yichang, 443001, China.
Department of Interventional Catheter Lab, Affiliated Renhe Hospital of China Three Gorges University, Yichang, 443001, China.
Mol Cell Biochem. 2024 Aug;479(8):2035-2045. doi: 10.1007/s11010-023-04811-2. Epub 2023 Jul 29.
Atherosclerosis (AS) is a dominant pathological basis of cardiovascular disease. Circular RNAs (circRNAs) have been proposed to have crucial functions in regulating pathological progressions of AS. Hence, the aim of this study was to investigate the potential function of circ_0090231 in AS progression. Oxidized low densitylipoprotein (ox-LDL)-challenged vascular smooth muscle cells (VSMCs) were used for in vitro functional analysis. Levels of genes and proteins were measured by qRT-PCR and Western blot. The proliferation, migration and invasion were assessed using cell counting kit-8, 5-ethynyl-2'-deoxyuridine, and transwell assays. The interaction between miR-942-5p and circ_0090231 or PPM1B (Protein Phosphatase, Mg/Mn Dependent 1B) was evaluated by dual-luciferase reporter and pull-down assays. Circ_0090231 is a stable circRNA, and was increased in the serum of AS patients and ox-LDL-challenged VSMCs. Functionally, silencing of circ_0090231 could reverse ox-LDL-induced proliferation, migration and invasion in VSMCs. Mechanistically, circ_0090231 directly targeted miR-942-5p, and PPM1B was a target of miR-942-5p. Besides, circ_0090231 sequestered miR-942-5p to release PPM1B expression, suggesting the circ_0090231/miR-942-5p/PPM1B axis. Further rescue experiments showed that miR-942-5p inhibition or ectopic overexpression of PPM1B dramatically attenuated the suppressing influences of circ_0090231 knockdown on VSMC proliferative, migratory and invasive abilities under ox-LDL treatment. Silencing of circ_0090231 could reverse ox-LDL-induced proliferation, migration and invasion in VSMCs via miR-942-5p/PPM1B axis, providing a theoretical basis for elucidating the mechanism of AS process.
动脉粥样硬化(AS)是心血管疾病的主要病理基础。环状 RNA(circRNAs)被认为在调节 AS 的病理进展中具有重要作用。因此,本研究旨在探讨 circ_0090231 在 AS 进展中的潜在功能。使用氧化低密度脂蛋白(ox-LDL)刺激的血管平滑肌细胞(VSMCs)进行体外功能分析。通过 qRT-PCR 和 Western blot 测量基因和蛋白质水平。使用细胞计数试剂盒-8、5-乙炔基-2'-脱氧尿苷和 Transwell 测定法评估增殖、迁移和侵袭。通过双荧光素酶报告和下拉测定评估 miR-942-5p 与 circ_0090231 或 PPM1B(蛋白磷酸酶,Mg/Mn 依赖性 1B)之间的相互作用。circ_0090231 是一种稳定的 circRNA,在 AS 患者的血清和 ox-LDL 刺激的 VSMCs 中增加。功能上,沉默 circ_0090231 可逆转 ox-LDL 诱导的 VSMCs 增殖、迁移和侵袭。机制上,circ_0090231 直接靶向 miR-942-5p,而 PPM1B 是 miR-942-5p 的靶标。此外,circ_0090231 可封闭 miR-942-5p 以释放 PPM1B 表达,提示 circ_0090231/miR-942-5p/PPM1B 轴。进一步的挽救实验表明,miR-942-5p 抑制或过表达 PPM1B 可显著减弱 ox-LDL 处理下 circ_0090231 敲低对 VSMC 增殖、迁移和侵袭能力的抑制作用。沉默 circ_0090231 可通过 miR-942-5p/PPM1B 轴逆转 ox-LDL 诱导的 VSMCs 增殖、迁移和侵袭,为阐明 AS 发生机制提供了理论依据。