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Construction and analysis of the lncRNA-miRNA-mRNA network based on competitive endogenous RNA reveals functional genes in heart failure

机译:基于竞争性内源RNA的lncRNA-miRNA-mRNA网络的构建和分析揭示了心力衰竭的功能基因

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摘要

Heart failure (HF) is a principal cause of morbidity and mortality worldwide, affecting an estimated 38 million people. Although significant progress has been made with respect to the underlying molecular mechanisms, the role of the competing endogenous RNA (ceRNA) network in the pathogenesis of HF remains largely unknown. In this study, an HF-associated ceRNA network was constructed based on the differentially expressed long noncoding RNAs (lncRNAs), microRNAs (miRNAs) and mRNAs obtained, respectively, from the , and datasets. The ceRNA network consisted of 12 lncRNA nodes, 43 miRNA nodes, 343 mRNA nodes and 530 edges. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that the ceRNA network was primarily enriched in the immune response, inflammatory response and T cell and B cell receptor signaling pathways. In addition, three lncRNAs (growth arrest specific 5, taurine upregulated 1 and HOX transcript antisense RNA) and three miRNAs [hsa-miRNA (miR)-26b-5p, hsa-miR-8485 and hsa-miR-940] with higher node degrees compared with other genes were selected as hub nodes. The expression of hub nodes in patients with HF was verified by reverse transcription-quantitative polymerase chain reaction analysis. The present study provided further insights into the important roles of the ceRNA network in HF development, and indicated the potential use of these hub nodes as diagnostic biomarkers and therapeutic targets.
机译:心力衰竭(HF)是全球发病率和死亡率的主要原因,估计有3800万人受到影响。尽管在潜在的分子机制方面已取得重大进展,但竞争性内源性RNA(ceRNA)网络在HF发病机理中的作用仍然未知。在这项研究中,基于分别从和数据集获得的差异表达的长非编码RNA(lncRNA),微小RNA(miRNA)和mRNA,构建了与HF相关的ceRNA网络。 ceRNA网络由12个lncRNA节点,43个miRNA节点,343个mRNA节点和530个边缘组成。基因本体论和《京都议定书》的基因与基因组百科全书通路分析表明,ceRNA网络主要丰富了免疫应答,炎症应答以及T细胞和B细胞受体的信号传导途径。此外,三个lncRNA(生长停滞特异性5,牛磺酸上调1和HOX转录反义RNA)和三个miRNA [hsa-miRNA(miR)-26b-5p,hsa-miR-8485和hsa-miR-940]选择与其他基因相比度为中心的节点。通过逆转录-定量聚合酶链反应分析验证了HF患者中枢节点的表达。本研究提供了对ceRNA网络在HF发育中的重要作用的进一步见解,并指出了这些集线器节点作为诊断性生物标志物和治疗靶标的潜在用途。

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