The circ_UBR4 (hsa_circ_0010283) is a novel abnormally overexpressed circRNA in oxidized low-density lipoprotein (ox-LDL)-induced model of atherosclerosis (AS) in human vascular smooth muscle cells (VSMCs). However, its role in the dysfunction of VSMCs remains to be further investigated. Here, we attempted to explore its role in ox-LDL-induced excessive proliferation and migration in VSMCs by regulating Rho/Rho-associated coiled-coil containing kinase 1 (ROCK1), a therapeutic target of AS. Expression of circ_UBR4 and ROCK1 was upregulated, whereas miR-107 was downregulated in human AS serum and ox-LDL-induced VSMCs. Depletion of circ_UBR4 arrested cell cycle, suppressed cell viability, colony-forming ability, and migration ability, and depressed expression of proliferating cell nuclear antigen and matrix metalloproteinase 2 in VSMCs in spite of the opposite effects of ox-LDL. Notably, ROCK1 upregulation mediated by plasmid transfection or miR-107 deletion could counteract the suppressive role of circ_UBR4 knockdown in ox-LDL-induced VSMCs proliferation, migration, and cell cycle progression. In mechanism, miR-107 was identified as a target of circ_UBR4 to mediate the regulatory effect of circ_UBR4 on ROCK1. circ_UBR4 might be a contributor in human AS partially by regulating VSMCs’ cell proliferation, migration, and cell cycle progression via circ_UBR4/miR-107/ROCK1 pathway.

中文翻译：

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阻断circ_UBR4可抑制动脉粥样硬化中人血管平滑肌细胞的增殖，迁移和细胞周期进程

circ_UBR4（hsa_circ_0010283）是一种氧化的低密度脂蛋白（ox-LDL）诱导的人血管平滑肌细胞（VSMC）动脉粥样硬化（AS）模型中异常表达异常的新型circRNA。但是，其在VSMC功能障碍中的作用有待进一步研究。在这里，我们试图通过调节含有Rho / Rho的含有AS 1的激酶1（ROCK1）的卷曲螺旋来探索其在VSMC中ox-LDL诱导的过度增殖和迁移中的作用。在人类AS血清和ox-LDL诱导的VSMC中，circ_UBR4和ROCK1的表达上调，而miR-107的表达下调。circ_UBR4耗竭可阻止细胞周期，抑制细胞活力，集落形成能力和迁移能力，尽管ox-LDL具有相反的作用，但VSMC中增殖细胞核抗原和基质金属蛋白酶2的表达仍呈下降趋势。值得注意的是，质粒转染或miR-107缺失介导的ROCK1上调可以抵消circ_UBR4敲低对ox-LDL诱导的VSMC增殖，迁移和细胞周期进程的抑制作用。在机制上，miR-107被鉴定为circ_UBR4的靶标，以介导circ_UBR4对ROCK1的调节作用。circ_UBR4可能通过circ_UBR4 / miR-107 / ROCK1途径调节VSMC的细胞增殖，迁移和细胞周期进程，部分地是人类AS的贡献者。质粒转染或miR-107缺失介导的ROCK1上调可以抵消circ_UBR4敲低对ox-LDL诱导的VSMC增殖，迁移和细胞周期进程的抑制作用。在机制上，miR-107被鉴定为circ_UBR4的靶标，以介导circ_UBR4对ROCK1的调节作用。circ_UBR4可能通过circ_UBR4 / miR-107 / ROCK1途径调节VSMC的细胞增殖，迁移和细胞周期进程，部分地是人类AS的贡献者。质粒转染或miR-107缺失介导的ROCK1上调可以抵消circ_UBR4敲低对ox-LDL诱导的VSMC增殖，迁移和细胞周期进程的抑制作用。在机制上，miR-107被鉴定为circ_UBR4的靶标，以介导circ_UBR4对ROCK1的调节作用。circ_UBR4可能通过circ_UBR4 / miR-107 / ROCK1途径调节VSMC的细胞增殖，迁移和细胞周期进程，部分地是人类AS的贡献者。