Circular RNA (circRNAs) has been confirmed to participate in atherosclerosis (AS) progression. However, the role and mechanism of hsa_circ_0032389 in AS process still need to be further revealed. This study evaluates the role and mechanism of hsa_circ_0032389 in AS process. Platelet-derived growth factor-BB (PDGF-BB) was used to induce human aortic vascular smooth muscle cells (HA-VSMCs). The expression levels of hsa_circ_0032389, microRNA (miR)-513a-5p, and fibroblast growth factor receptor substrate 2 (FRS2) were examined by quantitative real-time PCR. Cell proliferation and migration were analyzed using cell counting kit 8 assay, flow cytometry, EdU assay, transwell assay, and wound healing assay. Protein expression was assessed using western blot analysis. Dual-luciferase reporter and RIP assays were used to confirm RNA interaction. Hsa_circ_0032389 was overexpressed in PDGF-BB-induced HA-VSMCs, and its downregulation inhibited HA-VSMC viability, cell cycle, EdU positive cell rate, migratory cell number, and wound closure rate under PDGF-BB treatment. The luciferase activity of hsa_circ_0032389^wt could be reduced by miR-513a-5p mimic, and both hsa_circ_0032389 and miR-513a-5p were enriched in anti-Ago2, confirming that miR-513a-5p could be sponged by hsa_circ_0032389. MiR-513a-5p inhibitor reversed the effect of hsa_circ_0032389 knockdown on PDGF-BB-induced HA-VSMC viability, cell cycle, EdU positive cell rate, migratory cell number, and wound closure rate. Moreover, the luciferase activity of FRS2^wt was reduced by miR-513a-5p mimic, and both FRS2 and miR-513a-5p were enriched in anti-Ago2, verifying that FRS2 was targeted by miR-513a-5p. MiR-513a-5p suppressed PDGF-BB-induced HA-VSMC viability, cell cycle, EdU positive cell rate, migratory cell number, and wound closure rate by targeting FRS2. Our results indicated that hsa_circ_0032389 enhanced PDGF-BB-induced HA-VSMC proliferation and migration via regulating miR-513a-5p/FRS2 axis.

环状RNA（circRNA）已被证实参与动脉粥样硬化（AS）的进展。但hsa_circ_0032389在AS过程中的作用和机制仍需进一步揭示。本研究评估了 hsa_circ_0032389 在 AS 过程中的作用和机制。血小板衍生生长因子-BB (PDGF-BB) 用于诱导人主动脉血管平滑肌细胞 (HA-VSMC)。通过实时定量 PCR 检查 hsa_circ_0032389、microRNA (miR)-513a-5p 和成纤维细胞生长因子受体底物 2 (FRS2) 的表达水平。使用细胞计数试剂盒8测定、流式细胞术、EdU测定、transwell测定和伤口愈合测定来分析细胞增殖和迁移。使用蛋白质印迹分析评估蛋白质表达。双荧光素酶报告基因和 RIP 测定用于确认 RNA 相互作用。Hsa_circ_0032389 在 PDGF-BB 诱导的 HA-VSMC 中过表达，其下调会抑制 PDGF-BB 治疗下的 HA-VSMC 活力、细胞周期、EdU 阳性细胞率、迁移细胞数和伤口闭合率。miR-513a-5p模拟物可以降低hsa_circ_0032389 wt的荧光素酶活性，并且hsa_circ_0032389和miR-513a-5p都富集抗Ago2，证实miR-513a-5p可以被hsa_circ_0032389海绵^化。MiR-513a-5p 抑制剂逆转了 hsa_circ_0032389 敲低对 PDGF-BB 诱导的 HA-VSMC 活力、细胞周期、EdU 阳性细胞率、迁移细胞数和伤口闭合率的影响。此外，miR-513a-5p模拟物降低了FRS2 ^wt的荧光素酶活性，并且FRS2和miR-513a-5p均富含抗Ago2，验证了FRS2是miR-513a-5p的靶标。MiR-513a-5p 通过靶向 FRS2 抑制 PDGF-BB 诱导的 HA-VSMC 活力、细胞周期、EdU 阳性细胞率、迁移细胞数和伤口闭合率。我们的结果表明 hsa_circ_0032389 通过调节 miR-513a-5p/FRS2 轴增强 PDGF-BB 诱导的 HA-VSMC 增殖和迁移。