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环状 RNA_RUSC2 上调 miR-661 靶基因的表达,并调节血管平滑肌细胞的功能。

Circ_RUSC2 upregulates the expression of miR-661 target gene and regulates the function of vascular smooth muscle cells.

机构信息

Department of Cardiology, Linyi Central Hospital, Linyi 276400, China.

出版信息

Biochem Cell Biol. 2019 Dec;97(6):709-714. doi: 10.1139/bcb-2019-0031. Epub 2019 Jun 14.

Abstract

Many studies have identified circRNA as a prospective direction in the field of cardiovascular research. Detection of circRNA expression in different vascular smooth muscle cell (VSMC) phenotypes revealed that circ_RUSC2 is upregulated in proliferative VSMCs. Sequence analysis of circ_RUSC2 showed that there are multiple binding sites of miR-661 on circ_RUSC2, and that is an important target gene of miR-661. MiR-661 expression is downregulated in proliferative VSMCs, whereas the expression of SYK is upregulated. Circ_RUSC2 and miR-661 do not affect each other's expression levels, but circ_RUSC2 can promote the expression of SYK and inhibit the expression of SM22-alpha, whereas miR-661 has the opposite effect. At the same time, VSMC proliferation and migration can be promoted by SYK or circ_RUSC2, but the linear sequence of circ_RUSC2 can not. MiR-661 and circ_RUSC2 siRNAs inhibit VSMC proliferation and migration, and promote cell apoptosis. When an miR-661 mimic or SYK siRNAs were co-transfected with circ_RUSC2 overexpression vector, VSMC proliferation, apoptosis, and migration were not significantly altered. Accordingly, circ_RUSC2 can promote the expression of , a target gene of miR-661, and regulate VSMC proliferation, apoptosis, phenotypic modulation, and migration. These findings will supply a theoretical basis for studying circRNA function in VSMCs, and new ideas for the diagnosis and treatment of cardiovascular diseases.

摘要

许多研究已经将 circRNA 鉴定为心血管研究领域的一个有前景的方向。检测不同血管平滑肌细胞(VSMC)表型中的 circRNA 表达,发现 circ_RUSC2 在增殖性 VSMC 中上调。circ_RUSC2 的序列分析表明,circ_RUSC2 上有多个 miR-661 的结合位点,是 miR-661 的一个重要靶基因。miR-661 在增殖性 VSMC 中表达下调,而 SYK 的表达上调。circ_RUSC2 和 miR-661 不影响彼此的表达水平,但 circ_RUSC2 可以促进 SYK 的表达并抑制 SM22-alpha 的表达,而 miR-661 则有相反的作用。同时,SYK 或 circ_RUSC2 可以促进 VSMC 的增殖和迁移,但 circ_RUSC2 的线性序列则不能。miR-661 和 circ_RUSC2 siRNAs 抑制 VSMC 的增殖和迁移,并促进细胞凋亡。当共转染 miR-661 模拟物或 SYK siRNAs 与 circ_RUSC2 过表达载体时,VSMC 的增殖、凋亡和迁移没有明显改变。因此,circ_RUSC2 可以促进 miR-661 的靶基因 的表达,并调节 VSMC 的增殖、凋亡、表型调节和迁移。这些发现将为研究 circRNA 在 VSMCs 中的功能提供理论基础,并为心血管疾病的诊断和治疗提供新的思路。

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