Comprehensive circRNA expression profile and construction of circRNA-related ceRNA network in cardiac fibrosis
Comprehensive circRNA expression profile and construction of circRNA-related ceRNA network in cardiac fibrosis
复制标题
心脏纤维化中circRNA的综合表达谱和circRNA相关ceRNA网络的构建
DOI：
10.1016/j.biopha.2020.109944
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发表时间：
2020-05-01
影响因子：
7.5
通讯作者：
Zhang, Yao
中科院分区：
文献类型：
--
作者：
Gu, Xia;Jiang, Ya-Nan;Zhang, Yao
心脏纤维化是一种常见的病理状态，导致许多心脏疾病的进展。环状RNA（circRNA）正在成为心脏纤维化的新调控因子。然而，circRNA在心脏纤维化中的表达和功能在很大程度上仍然未知。本研究旨在研究circRNA的表达谱并确定circRNA在心脏纤维化中的作用。转化生长因子-β 1（TGF-β 1）用于在心脏成纤维细胞中建立心脏纤维化的体外模型。CircRNA测序显示，在纤维化心脏成纤维细胞中总共有283个circRNA异常表达，其中79个上调，204个下调。通过实时PCR验证随机选择的circRNA的表达变化。建立了一个基于circRNA的竞争性内源RNA网络1755个节点和30394条边，并使用插件MCODE进行模块分析。对前三个富集模块中涉及的mRNA进行KEGG途径富集分析。结果表明，这些mRNA在心脏纤维化相关的信号通路中富集，包括“TGF-β信号通路”、“MAPK信号通路"、”AMPK信号通路“和”PI 3 K-Akt信号通路“。预测的ceRNA和生物信息学分析揭示了circRNA在心脏纤维化中的潜在作用，为了解心脏纤维化的机制和寻找有效的防治靶点提供了有用的信息。
Cardiac fibrosis is a common pathological condition that contributes to the progression of many cardiac diseases. Circular RNAs (circRNAs) are emerging as new regulators of cardiac fibrosis. However, the expression and function of circRNAs in cardiac fibrosis remain largely unknown. The present study aims to investigate the circRNA expression profile and identify the roles of circRNAs in cardiac fibrosis. Transforming growth factor-beta 1 (TGF-beta 1) was used to establish an in vitro model of cardiac fibrosis in cardiac fibroblasts. CircRNA sequencing revealed that a total of 283 circRNAs were aberrantly expressed in fibrotic cardiac fibroblasts, with 79 upregulated and 204 downregulated. The expression changes of randomly selected circRNAs were validated by real-time PCR. A circRNA-based competing endogenous RNA network 1755 nodes and 30394 edges was established, and module analysis was conducted using the plug-in MCODE. KEGG pathway enrichment analysis was performed for mRNAs involved in the top three enriched modules. The results showed that these mRNAs were enriched in cardiac fibrosis-related signalling pathways, including the 'TGF-beta signaling pathway', 'MAPK signaling pathway', 'AMPK signaling pathway', and 'PI3K-Akt signaling pathway'. The predicted ceRNAs and bioinformatics analysis revealed the potential role of circRNAs in cardiac fibrosis, which would provide useful information for understanding the mechanism and finding effective prevention and treatment targets for cardiac fibrosis.