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首页> 外文期刊>Journal of cellular and molecular medicine. >LncRNA‐mRNA competing endogenous RNA network depicts transcriptional regulation in ischaemia reperfusion injury
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LncRNA‐mRNA competing endogenous RNA network depicts transcriptional regulation in ischaemia reperfusion injury

机译:LncRNA-mRNA竞争内源性RNA网络描述了缺血再灌注损伤中的转录调控

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摘要

The study aimed to investigate time‐course transcriptomes in myocardial ischaemia reperfusion injury (IRI) via RNA‐Seq. Transcriptomes of 10 samples derived from patients with acute ST‐segment elevation myocardial infarction (ASTEMI) who were assigned to percutaneous coronary intervention (PCI), were sequenced at the time of 0 (before PCI), 2, 12, 24 and 72?hours after PCI, respectively. Using the genefilter package in r , wgcna and stem , different expression lncRNA (DEL) and mRNA (DEM) were analysed. Out of 756 mRNAs and 206 lncRNAs shared by enrolled patients, 135 RNAs were screened to be significantly associated with the IRI. Furthermore, combined with lncRNA‐mRNA, lncRNA‐miRNA and miRNA‐mRNA network, 51 RNAs and 131 relationship pairs were ascertained in the competing endogenous RNAs (ceRNA) network. Among these nodes, SH2D3C and GTF2H4 were significantly enriched in cellular response to stress and their interaction module were isolated from functional ceRNA network. Subsequently, their critical role was confirmed via down‐regulation of SH2D3C and GTF2H4 expression in vitro model. These results identified that lncRNA‐mRNA ceRNA network, associated significantly with IRI, functioned as critical regulative pivotal roles after PCI‐AMI, and SH2D3C and GTF2H4 may be the most responsive transcriptional regulator in the early‐phase of IRI.
机译:该研究旨在研究通过RNA‐Seq在心肌缺血再灌注损伤(IRI)中的时程转录组。在0(PCI之前),2、12、24和72小时的时间对10份来自急性ST段抬高型心肌梗死(ASTEMI)患者的样本进行转录组测序,这些样本被分配用于经皮冠状动脉介入治疗(PCI)。在PCI之后。使用r,wgcna和stem中的genefilter软件包,分析了不同表达的lncRNA(DEL)和mRNA(DEM)。在入组患者共有的756个mRNA和206个lncRNA中,筛选出135个与IRI显着相关的RNA。此外,结合lncRNA-mRNA,lncRNA-miRNA和miRNA-mRNA网络,在竞争性内源RNA(ceRNA)网络中确定了51个RNA和131个关系对。在这些节点中,SH2D3C和GTF2H4显着丰富了细胞对应激的反应,并从功能性ceRNA网络中分离了它们的相互作用模块。随后,通过在体外模型中下调SH2D3C和GTF2H4表达,证实了它们的关键作用。这些结果表明,与IRI显着相关的lncRNA-mRNA ceRNA网络在PCI-AMI之后起着关键的关键调节作用,而SH2D3C和GTF2H4可能是IRI早期响应最迅速的转录调节因子。

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