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长链非编码 RNA 在心血管疾病中的生物学功能及潜在机制。

The biological function and potential mechanism of long non-coding RNAs in cardiovascular disease.

机构信息

Institute of Cardiovascular Disease Research, Xuzhou Medical University, Xuzhou, China.

Department of Cardiology, Xuzhou Central Hospital, Xuzhou, China.

出版信息

J Cell Mol Med. 2020 Nov;24(22):12900-12909. doi: 10.1111/jcmm.15968. Epub 2020 Oct 13.

Abstract

Long non-coding RNAs (lncRNAs), as part of the family of non-protein-coding transcripts, are implicated in the occurrence and progression of several cardiovascular diseases (CVDs). With recent advances in lncRNA research, these molecules are purported to regulate gene expression at multiple levels, thereby producing beneficial or detrimental biological effects during CVD pathogenesis. At the transcriptional level, lncRNAs affect gene expression by interacting with DNA and proteins, for example, components of chromatin-modifying complexes, or transcription factors affecting chromatin status. These potential mechanisms suggest that lncRNAs guide proteins to specific gene loci (eg promoter regions), or forestall proteins to specific genomic sites via DNA binding. Additionally, some lncRNAs are required for correct chromatin conformation, which occurs via chromatin looping in enhancer-like models. At the post-transcriptional level, lncRNAs interact with RNA molecules, mainly microRNAs (miRNAs) and mRNAs, potentially regulating CVD pathophysiological processes. Moreover, lncRNAs appear to post-transcriptionally modulate gene expression by participating in mRNA splicing, stability, degradation and translation. Thus, the purpose of this review is to provide a comprehensive summary of lncRNAs implicated in CVD biological processes, with an emphasis on potential mechanisms of action.

摘要

长链非编码 RNA(lncRNA)作为非蛋白编码转录本家族的一部分,与多种心血管疾病(CVD)的发生和发展有关。随着 lncRNA 研究的最新进展,这些分子据称可以在多个水平上调节基因表达,从而在 CVD 发病机制中产生有益或有害的生物学效应。在转录水平上,lncRNA 通过与 DNA 和蛋白质相互作用影响基因表达,例如,染色质修饰复合物的组成部分或影响染色质状态的转录因子。这些潜在的机制表明,lncRNA 通过 DNA 结合将蛋白质引导到特定的基因座(例如启动子区域),或者阻止蛋白质到达特定的基因组位点。此外,一些 lncRNA 对于正确的染色质构象是必需的,这种构象通过增强子样模型中的染色质环化发生。在转录后水平上,lncRNA 与 RNA 分子(主要是 microRNA(miRNA)和 mRNA)相互作用,可能调节 CVD 病理生理过程。此外,lncRNA 似乎通过参与 mRNA 剪接、稳定性、降解和翻译来在转录后水平上调节基因表达。因此,本综述的目的是全面总结与 CVD 生物学过程相关的 lncRNA,重点介绍潜在的作用机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c78a/7701533/d3910d17dd86/JCMM-24-12900-g001.jpg

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