Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, PR China; Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin Medical University, Harbin, 150086, PR China; Department of Cardiology, The Heilongjiang Provincial Hospital, Harbin, PR China.
Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, PR China; College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, PR China.
Biomed Pharmacother. 2020 May;125:109944. doi: 10.1016/j.biopha.2020.109944. Epub 2020 Feb 12.
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-β1 (TGF-β1) 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.
心脏纤维化是一种常见的病理状况，可导致许多心脏疾病的进展。环状 RNA（circRNA）作为心脏纤维化的新调节因子而出现。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。本研究旨在调查 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-β1（TGF-β1）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，纤维化的心脏成纤维细胞中共有 283 个 circRNA 表达异常，其中 79 个上调，204 个下调。通过实时 PCR 验证了随机选择的 circRNA 的表达变化。建立了基于 circRNA 的竞争性内源 RNA 网络，共有 1755 个节点和 30394 个边缘，并使用插件 MCODE 进行了模块分析。对 top3 富集模块中涉及的 mRNAs 进行了 KEGG 通路富集分析。结果表明，这些 mRNAs 富集在与心脏纤维化相关的信号通路中，包括“TGF-β 信号通路”、“MAPK 信号通路”、“AMPK 信号通路”和“PI3K-Akt 信号通路”。预测的 ceRNA 及其生物信息学分析揭示了 circRNA 在心脏纤维化中的潜在作用，这将为理解机制和寻找心脏纤维化的有效预防和治疗靶点提供有用的信息。
