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急性病毒性心肌炎小鼠心脏中长链非编码RNA和信使RNA表达谱分析

Analysis of long noncoding RNAs and messenger RNAs expression profiles in the hearts of mice with acute viral myocarditis.

作者信息

Xue Yimin, Ke Jun, Zhang Jiuyun, Chen Mingguang, Zeng Lijuan, Fan Qiaolian, Zheng Chunfu, Chen Feng

机构信息

Fourth Department of Critical Care Medicine, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, Fujian, China.

Department of Emergency, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, Fujian, China.

出版信息

J Med Virol. 2023 Feb;95(2):e28473. doi: 10.1002/jmv.28473.

Abstract

Acute viral myocarditis (AVMC) is a common acute myocardial inflammation caused by viral infections, which can lead to severe cardiac dysfunction. Several long noncoding RNAs (lncRNAs) with aberrant expression have been identified in the pathogenesis of AVMC. However, the expression profiles and functions of lncRNAs in AVMC have not been fully elucidated. In the present study, we constructed AVMC mouse models by intraperitoneal injection of coxsackievirus B3 (CVB3) and performed RNA sequencing (RNA-seq) on heart tissues to investigate the differences in lncRNAs and messenger RNAs (mRNAs) expression profiles. Based on the cutoff criteria of adjusted p-values (padj) <0.05 and |log2FoldChange| >1, a total of 1122 differentially expressed lncRNAs (DElncRNAs) and 3186 differentially expressed mRNAs (DEmRNAs) were screened, including 734 upregulated and 388 downregulated lncRNAs, 1821 upregulated and 1365 downregulated mRNAs. RT-qPCR analysis validated that the expression patterns of 12 randomly selected genes (6 DElncRNAs and 6 DEmRNAs) were highly consistent with those in RNA-seq, proving the reliability of the RNA-seq data. Then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that differentially expressed genes were mainly involved in metabolic and immune-related processes. Furthermore, co-expression networks between DElncRNAs and DEmRNAs in cytokine-cytokine receptor interaction, MAPK signaling pathway, and PI3K-Akt signaling pathway were constructed to study the molecular interactions of these molecules. Our study, for the first time, reveals the expression profiles of lncRNAs and mRNAs associated with AVMC, which may shed light on the roles of lncRNAs in disease pathogenesis and aid in discovering new therapeutic targets.

摘要

急性病毒性心肌炎(AVMC)是由病毒感染引起的常见急性心肌炎症,可导致严重的心功能障碍。在AVMC的发病机制中,已鉴定出几种表达异常的长链非编码RNA(lncRNA)。然而,AVMC中lncRNA的表达谱和功能尚未完全阐明。在本研究中,我们通过腹腔注射柯萨奇病毒B3(CVB3)构建了AVMC小鼠模型,并对心脏组织进行了RNA测序(RNA-seq),以研究lncRNA和信使RNA(mRNA)表达谱的差异。基于调整后p值(padj)<0.05和|log2倍变化|>1的截断标准,共筛选出1122个差异表达的lncRNA(DElncRNA)和3186个差异表达的mRNA(DEmRNA),其中包括734个上调和388个下调的lncRNA,1821个上调和1365个下调的mRNA。RT-qPCR分析验证了随机选择的12个基因(6个DElncRNA和6个DEmRNA)的表达模式与RNA-seq中的表达模式高度一致,证明了RNA-seq数据的可靠性。然后,基因本体论和京都基因与基因组百科全书富集分析表明,差异表达基因主要参与代谢和免疫相关过程。此外,构建了细胞因子-细胞因子受体相互作用、MAPK信号通路和PI3K-Akt信号通路中DElncRNA和DEmRNA之间的共表达网络,以研究这些分子的分子相互作用。我们的研究首次揭示了与AVMC相关的lncRNA和mRNA的表达谱,这可能有助于阐明lncRNA在疾病发病机制中的作用,并有助于发现新的治疗靶点。

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