Circular RNAs have been reported as vital regulators and promising therapeutic targets in multiple human diseases, including atherosclerosis (AS). However, the functional roles of circ_0010283 in AS remain unclear. The real-time quantitative polymerase chain reaction was used to determine the expression levels of circ_0010283, microRNA (miR)-377-3p, and cyclin D1 (CCND1) in serum samples. The vascular smooth muscle cells (VSMCs) were treated with oxidized low-density lipoprotein (ox-LDL) to establish the in vitro cell model of AS. The 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide and clonal colony-forming assays were performed to assess cell proliferation. The apoptosis was determined by flow cytometry assay. The migration of VSMCs was examined by wound healing and transwell assays. Western blot analysis was used to quantify protein expression. The association among circ_0010283, miR-377-3p, and CCND1 was confirmed by dual-luciferase reporter assay. We found that the serum level of circ_0010283 was upregulated in patients with AS and treatment with ox-LDL also increased the expression of circ_0010283 in VSMCs. Treatment with ox-LDL also increased proliferation, migration, and inflammation while inhibited apoptosis in VSMCs, which was overturned by silencing of circ_0010283. Moreover, miR-377-3p was a target of circ_0010283, and downregulation of miR-377-3p counteracted circ_0010283 silencing-induced effects on ox-LDL-stimulated VSMCs. The overexpression of miR-377-3p inhibited proliferation, migration, and inflammation while induced apoptosis of VSMCs by targeting CCND1. CCND1 was a target of miR-377-3p, and circ_0010283 acted as the miR-377-3p sponge to increase CCND1 expression. Circ_0010283 regulated proliferation, apoptosis, migration, and inflammation of ox-LDL-stimulated VSMCs through modulating miR-377-3p and CCND1.

中文翻译：

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Circ_0010283/miR-377-3p/Cyclin D1 轴与氧化的低密度脂蛋白刺激的血管平滑肌细胞的增殖、凋亡、迁移和炎症有关。

据报道，环状 RNA 在包括动脉粥样硬化 (AS) 在内的多种人类疾病中是重要的调节因子和有希望的治疗靶点。然而，circ_0010283 在 AS 中的功能作用仍不清楚。采用实时定量聚合酶链反应测定血清样品中circ_0010283、microRNA (miR)-377-3p和cyclin D1 (CCND1)的表达水平。用氧化低密度脂蛋白（ox-LDL）处理血管平滑肌细胞（VSMCs），建立AS体外细胞模型。进行 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium 溴化物和克隆集落形成测定以评估细胞增殖。通过流式细胞术测定细胞凋亡。通过伤口愈合和 transwell 测定检查 VSMC 的迁移。蛋白质印迹分析用于量化蛋白质表达。circ_0010283、miR-377-3p 和 CCND1 之间的关联通过双荧光素酶报告基因分析得到证实。我们发现，AS 患者的血清 circ_0010283 水平上调，并且 ox-LDL 治疗也增加了 VSMCs 中 circ_0010283 的表达。ox-LDL 治疗也增加了增殖、迁移和炎症，同时抑制了 VSMCs 的细胞凋亡，这被 circ_0010283 的沉默所推翻。此外，miR-377-3p 是 circ_0010283 的靶标，miR-377-3p 的下调抵消了 circ_0010283 沉默诱导的对 ox-LDL 刺激的 VSMC 的影响。miR-377-3p 的过表达抑制增殖、迁移和炎症，同时通过靶向 CCND1 诱导 VSMC 凋亡。CCND1 是 miR-377-3p 的靶标，circ_0010283 作为 miR-377-3p 海绵增加 CCND1 的表达。Circ_0010283 通过调节 miR-377-3p 和 CCND1 调节 ox-LDL 刺激的 VSMC 的增殖、凋亡、迁移和炎症。