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Integrative Analyses of Genes Associated With Right Ventricular Cardiomyopathy Induced by Tricuspid Regurgitation
Frontiers in Genetics ( IF 2.8 ) Pub Date : 2021-09-17 , DOI: 10.3389/fgene.2021.708275
Chengnan Tian 1, 2, 3 , Yanchen Yang 2, 4 , Yingjie Ke 5 , Liang Yang 1, 2 , Lishan Zhong 1, 2 , Zhenzhong Wang 2, 4 , Huanlei Huang 1, 2
Affiliation  

Tricuspid regurgitation (TR) induces right ventricular cardiomyopathy, a common heart disease, and eventually leads to severe heart failure and serious clinical complications. Accumulating evidence shows that long non-coding RNAs (lncRNAs) are involved in the pathological process of a variety of cardiovascular diseases. However, the regulatory mechanisms and functional roles of RNA interactions in TR-induced right ventricular cardiomyopathy are still unclear. Accordingly, we performed integrative analyses of genes associated with right ventricular cardiomyopathy induced by TR to study the roles of lncRNAs in the pathogenesis of this disease. In this study, we used high-throughput sequencing data of tissue samples from nine clinical cases of right ventricular myocardial cardiomyopathy induced by TR and nine controls with normal right ventricular myocardium from the Genotype-Tissue Expression database. We identified differentially expressed lncRNAs and constructed a protein-protein interaction and lncRNA-messenger RNA (mRNA) co-expression network. Furthermore, we determined hub lncRNA-mRNA modules related to right ventricular myocardial disease induced by TR and constructed a competitive endogenous RNA network for TR-induced right ventricular myocardial disease by integrating the interaction of lncRNA-miRNA-mRNA. In addition, we analyzed the immune infiltration using integrated data and the correlation of each immune-related gene with key genes of the integrated expression matrix. The present study identified 648 differentially expressed mRNAs, 201 differentially expressed miRNAs, and 163 differentially expressed lncRNAs. Protein-protein interaction network analysis confirmed that ADRA1A, AVPR1B, OPN4, IL-1B, IL-1A, CXCL4, ADCY2, CXCL12, GNB4, CCL20, CXCL8, and CXCL1 were hub genes. CTD-2314B22.3, hsa-miR-653-5p, and KIF17ceRNA; SRGAP3-AS2, hsa-miR-539-5p, and SHANK1; CERS6-AS1, hsa-miR-497-5p, and OPN4; INTS6-AS1, hsa-miR-4262, and NEURL1B; TTN-AS1, hsa-miR-376b-3p, and TRPM5; and DLX6-AS1, hsa-miR-346, and BIRC7 axes were obtained by constructing the ceRNA networks. Through the immune infiltration analysis, we found that the proportion of CD4 and CD8 T cells was about 20%, and the proportion of fibroblasts and endothelial cells was high. Our findings provide some insights into the mechanisms of RNA interaction in TR-induced right ventricular cardiomyopathy and suggest that lncRNAs are a potential therapeutic target for treating right ventricular myocardial disease induced by TR.



中文翻译:

三尖瓣返流致右心室心肌病相关基因的整合分析

三尖瓣反流 (TR) 诱发右心室心肌病,一种常见的心脏病,并最终导致严重的心力衰竭和严重的临床并发症。越来越多的证据表明,长链非编码RNA(lncRNA)参与了多种心血管疾病的病理过程。然而,RNA相互作用在TR诱导的右心室心肌病中的调节机制和功能作用尚不清楚。因此,我们对与 TR 诱导的右心室心肌病相关的基因进行了综合分析,以研究 lncRNA 在该疾病发病机制中的作用。在这项研究中,我们使用来自基因型-组织表达数据库的九个由 TR 诱导的右心室心肌病临床病例和九个具有正常右心室心肌的对照的组织样本的高通量测序数据。我们鉴定了差异表达的lncRNA,并构建了蛋白质-蛋白质相互作用和lncRNA-信使RNA(mRNA)共表达网络。此外,我们确定了与TR诱导的右心室心肌病相关的hub lncRNA-mRNA模块,并通过整合lncRNA-miRNA-mRNA的相互作用构建了TR诱导的右心室心肌病的竞争性内源性RNA网络。此外,我们使用集成数据分析了免疫浸润以及每个免疫相关基因与集成表达矩阵的关键基因的相关性。本研究鉴定了 648 个差异表达的 mRNA、201 个差异表达的 miRNA 和 163 个差异表达的 lncRNA。蛋白质-蛋白质相互作用网络分析证实,ADRA1A、AVPR1B、OPN4、IL-1B、IL-1A、CXCL4、ADCY2、CXCL12、GNB4、CCL20、CXCL8和CXCL1是枢纽基因。CTD-2314B22.3、hsa-miR-653-5p和KIF17ceRNA;SRGAP3-AS2、hsa-miR-539-5p 和 SHANK1;CERS6-AS1、hsa-miR-497-5p 和 OPN4;INTS6-AS1、hsa-miR-4262 和 NEURL1B;TTN-AS1、hsa-miR-376b-3p 和 TRPM5;通过构建ceRNA网络获得DLX6-AS1、hsa-miR-346和BIRC7轴。通过免疫浸润分析,我们发现CD4和CD8 T细胞比例约为20%,成纤维细胞和内皮细胞比例较高。

更新日期:2021-09-17
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