LncRNA-mRNA competing endogenous RNA network depicts transcriptional regulation in ischaemia reperfusion injury
LncRNA-mRNA competing endogenous RNA network depicts transcriptional regulation in ischaemia reperfusion injury
复制标题
LncRNA-mRNA竞争内源RNA网络描绘了缺血再灌注损伤中的转录调控
DOI：
10.1111/jcmm.14163
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发表时间：
2019-03-01
影响因子：
5.3
通讯作者：
Li, Hua
中科院分区：
文献类型：
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作者：
Liu, Hongying;Xu, Danping;Li, Hua
该研究旨在通过RNA-Seq研究心肌缺血再灌注损伤（IRI）的时程转录组。对10例急性st段抬高型心肌梗死（ASTEMI）患者经皮冠状动脉介入治疗（PCI）后的转录组进行测序，时间分别为PCI前0、2、12、24和72小时。利用基因筛选包在r、wgcna和stem中分析不同表达的lncRNA （DEL）和mRNA （DEM）。在入组患者共有的756种mrna和206种lncrna中，有135种rna被筛选为与IRI显著相关。进一步，结合lncRNA-mRNA、lncRNA-miRNA和miRNA-mRNA网络，在竞争内源rna （ceRNA）网络中确定了51种rna和131对关系。在这些节点中，SH2D3C和GTF2H4在细胞应激反应中显著富集，并且它们的相互作用模块从功能性ceRNA网络中分离出来。随后，通过体外模型下调SH2D3C和GTF2H4的表达，证实了它们的关键作用。这些结果表明，与IRI显著相关的lncRNA-mRNA ceRNA网络在PCI-AMI后发挥了关键的调节关键作用，而SH2D3C和GTF2H4可能是IRI早期最敏感的转录调节因子。
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.