Identification of microRNAs related to myocardial ischemic reperfusion injury
Identification of microRNAs related to myocardial ischemic reperfusion injury
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DOI：
10.1002/jcp.27795
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发表时间：
2019-07-01
影响因子：
5.6
通讯作者：
Zhong, Liang
中科院分区：
文献类型：
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作者：
Liu, Kang;Ma, Li;Zhong, Liang
以往的研究表明，microRNAs(MiRNAs)与心肌缺血再灌注(I/R)损伤的进展有关。然而，由于测序平台、对照选择和筛选条件的不同，得到的结果不一致。为了探索心肌I/R损伤发病机制中的关键miRNAs，开发预防心肌I/R损伤的miRNA诊断生物标志物，我们对公开的心肌I/R损伤miRNA表达数据进行了系统的分析，并研究了签名miRNA的功能。从Google Scholar网站上提取了17个具有代表性的心肌I/R损伤miRNA数据集，并进行了系统的生物信息学分析。用TargetScan软件预测miRNA靶基因，用David和TFACTS数据库对靶基因进行功能浓缩和转录因子结合分析。在本研究中，共鉴定了10个与心肌I/R损伤相关的标志性miRNAs，其中包括8个显著上调的miRNAs(miR-let-7b-3p、miR-let-7c-3p、miR-15b-3p、miR-195-3p、miR-21-5p、miR-214-5p、miR-24-3p和miR-320a)和两个显著下调的miRNAs(miR-126-5p和miR-499a-5p)。它们对心肌I/R损伤的影响不同。上调的靶基因表达的信号信使RNA主要参与GO：0000122的转录调控过程、RNA聚合酶II启动子的转录负调控等，而下调的信号信使RNA主要参与GO：0070534、蛋白K63相关的泛素化等。综上所述，我们鉴定了10个与心肌I/R损伤发病机制相关的标志性miRNAs，并揭示了它们的靶基因和转录因子，为心肌I/R损伤的潜在治疗靶点提供了新的靶点。
Previous studies have suggested that microRNAs (miRNAs) are associated with the progression of myocardial ischemic reperfusion (I/R) injury. However, inconsistent results have been obtained due to the differences in sequencing platform, control selection, and filtering conditions. To explore the key miRNAs in the pathogenesis of myocardial I/R injury and develop miRNA diagnostic biomarkers for myocardial I/R injury prevention, we performed a systematic analysis of publicly available myocardial I/R injury miRNA expression data and investigated the function of the signature miRNA. A total of 17 representative myocardial I/R injury miRNA datasets were extracted from the Google Scholar website and a systematic bioinformatics analysis was done. TargetScan software was used to predict the miRNA target genes, and functional enrichment and transcription factor binding analyses were performed on the target genes using the DAVID and Tfacts databases. In this study, a total of 10 signature miRNAs associated with myocardial I/R injury were identified, which included eight significantly upregulated miRNAs (miR-let-7b-3p, miR-let-7c-3p, miR-15b-3p, miR-195-3p, miR-21-5p, miR-214-5p, miR-24-3p, and miR-320a) and two significantly downregulated miRNAs (miR-126-5p and miR-499a-5p). They had different influences on myocardial I/R injury. The upregulated target gene-expressing signature messenger RNAs (mRNAs) were mainly involved in the transcriptional regulation process of GO: 0000122, negative regulation of transcription from RNA polymerase II promoter, and so on, while downregulated expression of signature mRNAs was mainly involved in GO:0070534, protein K63-linked ubiquitination, and so forth. To summarize, 10 signature miRNAs of myocardial I/R injury pathogenesis were identified and their target genes and transcription factors were revealed, suggesting the potential novel therapeutic targets for myocardial I/R injury.