长链非编码 RNA-mRNA 竞争性内源性 RNA 网络描绘了缺血再灌注损伤中的转录调控。
LncRNA-mRNA competing endogenous RNA network depicts transcriptional regulation in ischaemia reperfusion injury.
机构信息
Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Fudan University, Shanghai, China.
Shanghai Green Valley Pharmaceutical Company, Shanghai, China.
出版信息
J Cell Mol Med. 2019 Mar;23(3):2272-2276. doi: 10.1111/jcmm.14163. Epub 2019 Jan 18.
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.
本研究通过 RNA-Seq 旨在探讨心肌缺血再灌注损伤 (IRI) 的时间转录组。从接受经皮冠状动脉介入治疗 (PCI) 的急性 ST 段抬高型心肌梗死 (ASTEMI) 患者中获得的 10 个样本的转录组,分别在 PCI 前(0 小时)、PCI 后 2、12、24 和 72 小时进行测序。使用 r 中的 genefilter 包、wgcna 和 stem,分析不同表达的长链非编码 RNA (DEL) 和信使 RNA (DEM)。在纳入的患者中共有 756 个 mRNA 和 206 个 lncRNA 中,筛选出 135 个 RNA 与 IRI 显著相关。此外,通过结合 lncRNA-mRNA、lncRNA-miRNA 和 miRNA-mRNA 网络,在竞争内源性 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 显著富集在细胞应激反应中,其相互作用模块从功能 ceRNA 网络中分离出来。随后,通过在体外模型下调 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 后起着关键的调节作用,SH2D3C 和 GTF2H4 可能是 IRI 早期最敏感的转录调节因子。