Reconstruction and Analysis of the lncRNA-miRNA-mRNA Network Based on Competitive Endogenous RNA Reveal Functional lncRNAs in Dilated Cardiomyopathy
Reconstruction and Analysis of the lncRNA-miRNA-mRNA Network Based on Competitive Endogenous RNA Reveal Functional lncRNAs in Dilated Cardiomyopathy
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DOI：
10.3389/fgene.2019.01149
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发表时间：
2019-11-15
影响因子：
3.7
通讯作者：
Yang, Xiaoyu
中科院分区：
文献类型：
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作者：
Tao, Lichan;Yang, Ling;Yang, Xiaoyu
扩张型心肌病(DCM)是导致猝死和心力衰竭的重要原因，病因不明。最近的研究表明，长非编码RNA(LncRNA)可以与microRNA(MiRNA)相互作用，也可以通过竞争性内源性RNA(Cerna)与mRNA间接相互作用。然而，CELNA在DCM中的作用机制尚不清楚。在这项研究中，首先使用扩张型心肌病患者和健康对照的心脏样本进行了miRNA阵列。为了进一步验证，我们使用DCM患者和阿霉素诱导的心肌病啮齿动物模型进行实时定量逆转录(RT)-PCR，结果显示miR-144-3p和miR-451a下调，miR-21-5p上调。基于Cerna理论，我们利用国家生物技术信息中心基因表达总括图(NCBI-GEO)和我们的miRNA阵列的数据构建了一个全球三重网络。LncRNA-miRNA-mRNA网络由22个lncRNA节点、32个mRNA节点和11个miRNA节点组成。结果表明，针对miR-144/451的两个LncRNAs(NONHSAT001691和NONHSAT006358)与DCM高度相关。然后，对CERNA网络的簇模块和随机游走进行了分析，并确定了四个针对miR-21的LncRNAs，它们与扩张型心肌病显著相关。本研究为扩张型心肌病或其他疾病的研究提供了新的策略。此外，lncRNA-miRNA对可作为DCM的候选诊断生物标志物或潜在的治疗靶点。
Dilated cardiomyopathy (DCM) is an important cause of sudden death and heart failure with an unknown etiology. Recent studies have suggested that long non-coding RNA (lncRNA) can interact with microRNA (miRNA) and indirectly interact with mRNA through competitive endogenous RNA (ceRNA) activities. However, the mechanism of ceRNA in DCM remains unclear. In this study, a miRNA array was first performed using heart samples from DCM patients and healthy controls. For further validation, we conducted real-time quantitative reverse transcription (RT)-PCR using samples from DCM patients and a doxorubicin-induced rodent model of cardiomyopathy, revealing that miR-144-3p and miR-451a were down-regulated, and miR-21-5p was up-regulated. Based on the ceRNA theory, we constructed a global triple network using data from the National Center for Biotechnology Information Gene Expression Omnibus (NCBI-GEO) and our miRNA array. The lncRNA-miRNA-mRNA network comprised 22 lncRNA nodes, 32 mRNA nodes, and 11 miRNA nodes. Hub nodes and the number of relationship pairs were then analyzed, and the results showed that two lncRNAs (NONHSAT001691 and NONHSAT006358) targeting miR-144/451 were highly related to DCM. Then, cluster module and random walk with restart for the ceRNA network were analyzed and identified four lncRNAs (NONHSAT026953/NONHSAT006250/NONHSAT133928/NONHSAT041662) targeting miR-21 that were significantly related to DCM. This study provides a new strategy for research on DCM or other diseases. Furthermore, lncRNA-miRNA pairs may be regarded as candidate diagnostic biomarkers or potential therapeutic targets of DCM.