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分析人类扩张型心肌病中环状 RNA 表达的变化及 ceRNA 网络的构建。

Analysis of changes in circular RNA expression and construction of ceRNA networks in human dilated cardiomyopathy.

机构信息

Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China.

Shanghai Institute of Cardiovascular Disease, Shanghai, China.

出版信息

J Cell Mol Med. 2021 Mar;25(5):2572-2583. doi: 10.1111/jcmm.16251. Epub 2021 Jan 22.

Abstract

Dilated cardiomyopathy (DCM) is a severe life-threatening disease worldwide, and the underlying mechanisms remain unclear. Circular RNAs (circRNAs) have been reported to play important roles in various cardiovascular diseases and can function as competitive endogenous RNAs (ceRNAs). However, their role in human DCM has not been fully elucidated. In the present study, heart samples from DCM patients and healthy controls were used to identify circRNAs by RNA sequencing. Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was conducted to validate differentially expressed circRNAs and mRNAs. A total of 9585 circRNAs and 22050 mRNAs were detected in the two groups. Overall, 213 circRNAs and 617 mRNAs were significantly up-regulated in the DCM group compared with the control group. Similarly, 85 circRNAs and 1125 mRNAs were significantly down-regulated. According to the ceRNA theory, circRNAs can indirectly interact with mRNAs by directly binding to microRNAs (miRNAs), and circRNAs and mRNAs should be concurrently either up-regulated or down-regulated. Based on this theory, we constructed two circRNA-miRNA-mRNA networks by using the RNA sequencing data and prediction by proprietary software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to probe the potential functions of differentially expressed circRNAs. In conclusion, this study revealed that the expression of cardiac circRNAs was altered in human DCM and explored the potential functions of circRNAs by constructing ceRNA networks. These findings provide a foundation for future studies of circRNAs in DCM.

摘要

扩张型心肌病(DCM)是一种严重的危及生命的全球性疾病,其潜在机制尚不清楚。环状 RNA(circRNA)已被报道在各种心血管疾病中发挥重要作用,并且可以作为竞争性内源 RNA(ceRNA)发挥作用。然而,它们在人类 DCM 中的作用尚未完全阐明。在本研究中,使用 RNA 测序鉴定 DCM 患者和健康对照者的心脏样本中的 circRNA。通过实时定量逆转录聚合酶链反应(qRT-PCR)验证差异表达的 circRNA 和 mRNA。在两组中总共检测到 9585 个 circRNA 和 22050 个 mRNA。总体而言,与对照组相比,DCM 组中有 213 个 circRNA 和 617 个 mRNA 显著上调。同样,85 个 circRNA 和 1125 个 mRNA 显著下调。根据 ceRNA 理论,circRNA 可以通过直接与 microRNA(miRNA)结合,间接与 mRNAs 相互作用,circRNA 和 mRNAs 应该同时上调或下调。基于这一理论,我们使用 RNA 测序数据和专有软件预测构建了两个 circRNA-miRNA-mRNA 网络。通过基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路分析来探究差异表达 circRNA 的潜在功能。总之,本研究揭示了人类 DCM 中心脏 circRNA 的表达发生改变,并通过构建 ceRNA 网络探讨了 circRNA 的潜在功能。这些发现为未来研究 DCM 中的 circRNA 提供了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec59/7933965/d024409d76d6/JCMM-25-2572-g001.jpg

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