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RNA 测序揭示扩张型心肌病中长链非编码 RNA 的全基因组特征。

RNA sequencing discloses the genome‑wide profile of long noncoding RNAs in dilated cardiomyopathy.

机构信息

Department of Cardiology, Liaocheng People's Hospital of Shandong University, Liaocheng, Shandong 252000, P.R. China.

Shandong Institute for Endemic Disease Control, Jinan, Shandong 250014, P.R. China.

出版信息

Mol Med Rep. 2019 Apr;19(4):2569-2580. doi: 10.3892/mmr.2019.9937. Epub 2019 Feb 5.

Abstract

Dilated cardiomyopathy (DCM) is a common type of non‑ischemic cardiomyopathy, of which the underlying mechanisms have not yet been fully elucidated. Long noncoding RNAs (lncRNAs) have been reported to serve crucial physiological roles in various cardiac diseases. However, the genome‑wide expression profile of lncRNAs remains to be elucidated in DCM. In the present study, a case‑control study was performed to identify expression deviations in circulating lncRNAs between patients with DCM and controls by RNA sequencing. Partial dysregulated lncRNAs were validated by reverse transcription‑polymerase chain reaction. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway, and lncRNA‑messenger RNA (mRNA) co‑expression network analyses were employed to probe potential functions of these dysregulated lncRNAs in DCM. Comparison between 8 DCM and 8 control samples demonstrated that there were alterations in the expression levels of 988 lncRNAs and 1,418 mRNAs in total. The dysregulated lncRNAs were found to be mainly associated with system development, organ morphogenesis and metabolic regulation in terms of 'biological processes'. Furthermore, the analysis revealed that the gap junction pathway, phagosome, and dilated and hypertrophic cardiomyopathy pathways may serve crucial roles in the development of DCM. The lncRNA‑mRNA co‑expression network also suggested that the target genes of the lncRNAs were different in patients with DCM as compared with those in the controls. In conclusion, the present study revealed the genome‑wide profile of circulating lncRNAs in DCM by RNA sequencing, and explored the potential functions of these lncRNAs in DCM using bioinformatics analysis. These findings provide a theoretical foundation for future studies of lncRNAs in DCM.

摘要

扩张型心肌病(DCM)是一种常见的非缺血性心肌病,其潜在机制尚未完全阐明。长链非编码 RNA(lncRNA)已被报道在各种心脏疾病中发挥重要的生理作用。然而,DCM 中 lncRNA 的全基因组表达谱仍有待阐明。本研究通过 RNA 测序进行了病例对照研究,以确定 DCM 患者与对照组之间循环 lncRNA 的表达差异。通过逆转录-聚合酶链反应验证了部分失调的 lncRNA。采用基因本体论、京都基因与基因组百科全书通路和 lncRNA-信使 RNA(mRNA)共表达网络分析探讨这些失调的 lncRNA 在 DCM 中的潜在功能。对 8 个 DCM 和 8 个对照样本进行比较,结果显示,总共有 988 个 lncRNA 和 1418 个 mRNA 的表达水平发生了改变。失调的 lncRNA 主要与“生物过程”中的系统发育、器官形态发生和代谢调节有关。此外,分析表明间隙连接途径、吞噬体、扩张和肥厚性心肌病途径可能在 DCM 的发展中发挥关键作用。lncRNA-mRNA 共表达网络还表明,与对照组相比,DCM 患者的 lncRNA 靶基因不同。总之,本研究通过 RNA 测序揭示了 DCM 循环 lncRNA 的全基因组图谱,并通过生物信息学分析探讨了这些 lncRNA 在 DCM 中的潜在功能。这些发现为未来研究 DCM 中的 lncRNA 提供了理论基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ae1/6423559/d482c7dab93d/MMR-19-04-2569-g00.jpg

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