Upregulation of Circular RNA CircNFIB Attenuates Cardiac Fibrosis by Sponging miR-433
Upregulation of Circular RNA CircNFIB Attenuates Cardiac Fibrosis by Sponging miR-433
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环状 RNA CircNFIB 的上调通过海绵 miR-433 减轻心脏纤维化
DOI：
10.3389/fgene.2019.00564
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发表时间：
2019-06-20
影响因子：
3.7
通讯作者：
Wang, Lijun
中科院分区：
文献类型：
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作者：
Zhu, Yujiao;Pan, Wen;Wang, Lijun
心肌纤维化是成纤维细胞增殖和成纤维细胞向肌成纤维细胞转化的病理结果。作为一类新的内源性非编码RNA，环状RNAs(CircRNAs)在包括纤维化在内的多种心血管疾病中被发现，通常作为microRNA(MiRNA)海绵发挥作用。在这里，我们报告了在小鼠心肌梗死后心脏样本以及经转化生长因子-β处理的原代成人心脏成纤维细胞中CircRNA-CircNFIB的表达减少。EDU掺入实验表明，强制表达CircNFIB抑制了NIH/3T3细胞和原代成人成纤维细胞的增殖。相反，抑制CircNFIB可促进成纤维细胞的增殖。此外，CircNFIB被鉴定为miR-433内源性海绵。过表达CircNFIB可减弱miR-433模拟物的促增殖作用，而抑制CircNFIB的作用则相反。最后，CircNFIB的上调也逆转了miR-433靶基因和下游信号通路的表达水平。总而言之，CircNFIB对于预防心脏纤维化至关重要。NFIB-miR-433轴可能代表了一种治疗纤维化疾病的新途径。
Cardiac fibrosis is the pathological consequence of fibroblast proliferation and fibroblast-to-myofibroblast transition. As a new class of endogenous non-coding RNAs, circular RNAs (circRNAs) have been identified in many cardiovascular diseases including fibrosis, generally acting as microRNA (miRNA) sponges. Here, we report that the expression of circRNA-circNFIB was decreased in mice post-myocardial infarction heart samples, as well as in primary adult cardiac fibroblasts treated with TGF-beta. Forced expression of circNFIB decreased cell proliferation in both NIH/3T3 cells and primary adult fibroblasts as evidenced by EdU incorporation. Conversely, inhibition of circNFIB promoted adult fibroblast proliferation. Furthermore, circNFIB was identified as a miR-433 endogenous sponge. Overexpression of circNFIB could attenuate pro-proliferative effects induced by the miR-433 mimic while inhibition of circNFIB exhibited opposite results. Finally, upregulation of circNFIB also reversed the expression levels of target genes and downstream signaling pathways of miR-433. In conclusion, circNFIB is critical for protection against cardiac fibrosis. The circNFIB-miR-433 axis may represent a novel therapeutic approach for treatment of fibrotic diseases.