CircRNA_000203 enhances the expression of fibrosis-associated genes by derepressing targets of miR-26b-5p, Col1a2 and CTGF, in cardiac fibroblasts.
CircRNA_000203 enhances the expression of fibrosis-associated genes by derepressing targets of miR-26b-5p, Col1a2 and CTGF, in cardiac fibroblasts.
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CircRNA_000203 通过去抑制心脏成纤维细胞中 miR-26b-5p、Col1a2 和 CTGF 的靶标来增强纤维化相关基因的表达。
DOI：
10.1038/srep40342
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发表时间：
2017-01-12
影响因子：
4.6
通讯作者：
Shan ZX
中科院分区：
文献类型：
--
作者：
Tang CM;Zhang M;Huang L;Hu ZQ;Zhu JN;Xiao Z;Zhang Z;Lin QX;Zheng XL;-Yang M;Wu SL;Cheng JD;Shan ZX
环状RNA(CircRNAs)在不同的生物和病理过程中参与调节基因表达。本研究旨在探讨CircRNA_000203调控心脏成纤维细胞纤维化相关基因表达的机制。在糖尿病小鼠心肌和血管紧张素Ⅱ诱导的小鼠心脏成纤维细胞中，CircRNA_000203表达上调。增强表达CircRNA_000203可增加小鼠心脏成纤维细胞COL1a2、COL3a1和α-SMA的表达。核糖核酸下拉和RT-qPCR分析表明，CircRNA_000203能特异性地与miR-26b-5p结合。双荧光素酶报告基因分析表明miR-26b-5p能与Col1a2和CTF3‘UTRs相互作用，而CIRC_000203能阻断miR-26b-5p和Col1a2和CTGF3’UTRs之间的相互作用。转染miR-26b-5p可转录后抑制心脏成纤维细胞COL1a2和α-SmA的表达，同时抑制COL3a1和CTF1a的表达。此外，过表达CircRNA_000203可以消除miR-26b-5p对心脏成纤维细胞的抗纤维化作用。综上所述，我们的结果表明抑制miR-26b-5p的功能有助于CircRNA_000203在心脏成纤维细胞中的促纤维化作用。
Circular RNAs (circRNAs) participate in regulating gene expression in diverse biological and pathological processes. The present study aimed to investigate the mechanism underlying the modulation of circRNA_000203 on expressions of fibrosis-associated genes in cardiac fibroblasts. CircRNA_000203 was shown upregulated in the diabetic mouse myocardium and in Ang-II-induced mouse cardiac fibroblasts. Enforced-expression of circRNA_000203 could increase expressions of Col1a2, Col3a1 and α-SMA in mouse cardiac fibroblasts. RNA pull-down and RT-qPCR assay indicated that circRNA_000203 could specifically sponge miR-26b-5p. Dual luciferase reporter assay revealed that miR-26b-5p interacted with 3′UTRs of Col1a2 and CTGF, and circ_000203 could block the interactions of miR-26b-5p and 3′UTRs of Col1a2 and CTGF. Transfection of miR-26b-5p could post-transcriptionaly inhibit expressions of Col1a2 and CTGF, accompanied with the suppressions of Col3a1 and α-SMA in cardiac fibroblasts. Additionally, over-expression of circRNA_000203 could eliminate the anti-fibrosis effect of miR-26b-5p in cardiac fibroblasts. Together, our results reveal that suppressing the function of miR-26b-5p contributes to the pro-fibrosis effect of circRNA_000203 in cardiac fibroblasts.