CircRNA circCOL1A1 Acts as a Sponge of miR-30a-5p to Promote Vascular Smooth Cell Phenotype Switch through Regulation of Smad1 Expression
CircRNA circCOL1A1 Acts as a Sponge of miR-30a-5p to Promote Vascular Smooth Cell Phenotype Switch through Regulation of Smad1 Expression
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DOI：
10.1055/s-0042-1757875
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发表时间：
2021-09
影响因子：
6.7
通讯作者：
M. Ye;Q. Ni;Han Wang;Yuli Wang;Yongjie Yao;Yinan Li;Weilun Wang;Shuofei Yang;Jia-quan Chen;Lei Lv;Yiping Zhao;G. Xue;Xiangjiang Guo;Lan Zhang
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作者：
M. Ye;Q. Ni;Han Wang;Yuli Wang;Yongjie Yao;Yinan Li;Weilun Wang;Shuofei Yang;Jia-quan Chen;Lei Lv;Yiping Zhao;G. Xue;Xiangjiang Guo;Lan Zhang
血管平滑肌细胞的表型转换在动脉粥样硬化的发病过程中起重要作用。在VSMCs从收缩型向合成型转变的过程中，合成生物标志物胶原I型α 1链（COL1A1）基因的mRNA表达上调。COL1A1基因转录的非编码环状rna与VSMC表型改变和动脉粥样硬化的关系尚不清楚。在这里，我们报道了COL1A1环状RNA (circCOL1A1)，它在VSMCs中特异性表达，并在VSMCs表型改变期间上调。CircCOL1A1也可在血清或血浆中检测到。健康血管组织中CircCOL1A1表达较低，而在动脉粥样硬化患者中表达上调。通过离体和体外实验，我们发现circCOL1A1可以促进VSMC表型转换。机制分析表明circCOL1A1可能作为miR-30a-5p的竞争内源性RNA发挥其功能。circol1a1上调可改善miR-30a-5p对其靶标SMAD1的抑制作用，从而抑制转化生长因子-β (TGF-β)信号传导。我们的研究结果表明，circCOL1A1通过miR-30a-5p/SMAD1/TGF-β轴促进VSMCs的表型转换，它可能作为动脉粥样硬化的新标志物或作为动脉粥样硬化的治疗靶点。
Phenotypic switch of vascular smooth muscle cells (VSMCs) plays an important role in the pathogenesis of atherosclerosis. The mRNA expression of the synthetic biomarker Collagen Type I Alpha 1 Chain (COL1A1) gene is upregulated during the switch of VSMCs from the contractile to the synthetic phenotype. The association of noncoding circular RNAs transcribed by the COL1A1 gene with VSMC phenotype alteration and atherogenesis remains unclear. Here we reported a COL1A1 circular RNA (circCOL1A1) which is specifically expressed in VSMCs and is upregulated during phenotype alteration of VSMCs. CircCOL1A1 is also detectable in the serum or plasma. Healthy vascular tissues have a low expression of CircCOL1A1, while it is upregulated in atherosclerosis patients. Through ex vivo and in vitro assays, we found that circCOL1A1 can promote VSMC phenotype switch. Mechanistic analysis showed that circCOL1A1 may exert its function as a competing endogenous RNA of miR-30a-5p. Upregulation of circCOL1A1 ameliorates the inhibitory effect of miR-30a-5p on its target SMAD1, which leads to suppression of transforming growth factor-β (TGF-β) signaling. Our findings demonstrate that circCOL1A1 promotes the phenotype switch of VSMCs through the miR-30a-5p/SMAD1/TGF-β axis and it may serve as a novel marker of atherogenesis or as a therapeutic target for atherosclerosis.