Liu Jie, Zhu Guoguo, Xu Siya, Liu Shixin, Lu Qiping, Tang Zhongzhi
Department of Emergency, Wuhan General Hospital of People's Liberation Army of China, Wuhan, Hubei 430070, P.R. China.
Department of General Surgery, Wuhan General Hospital of People's Liberation Army of China, Wuhan, Hubei 430070, P.R. China.
Int J Mol Med. 2017 Dec;40(6):1719-1730. doi: 10.3892/ijmm.2017.3174. Epub 2017 Oct 5.
To investigate the regulation of endothelial cell (EC) microRNAs (miRNAs) altered by heat stress, miRNA microarrays and bioinformatics methods were used to determine changes in miRNA profiles and the pathophysiological characteristics of differentially expressed miRNAs. A total of 31 differentially expressed miRNAs were identified, including 20 downregulated and 11 upregulated miRNAs. Gene Ontology (GO) enrichment analysis revealed that the validated targets of the differentially expressed miRNAs were significantly enriched in gene transcription regulation. The pathways were also significantly enriched in the Kyoto Encyclopedia of Genes and Genomes analysis, and most were cancer-related, including the mitogen-activated protein kinase signaling pathway, pathways involved in cancer, the Wnt signaling pathway, the Hippo signaling pathway, proteoglycans involved in cancer and axon guidance. The miRNA-gene and miRNA‑GO network analyses revealed several hub miRNAs, genes and functions. Notably, miR‑3613-3p played a dominant role in both networks. MAP3K2, MGAT4A, TGFBR1, UBE2R2 and SMAD4 were most likely to be controlled by the altered miRNAs in the miRNA-gene network. The miRNA‑GO network analysis revealed significantly complicated associations between miRNAs and different functions, and that the significantly enriched functions targeted by the differentially expressed miRNAs were mostly involved in regulating gene transcription. The present study demonstrated that miRNAs are involved in the pathophysiology of heat-treated ECs. Understanding the functions of miRNAs may provide novel insights into the molecular mechanisms underlying the heat‑induced pathophysiology of ECs.
为了研究热应激对内皮细胞(EC)微小RNA(miRNA)的调控作用,采用miRNA芯片和生物信息学方法来确定miRNA表达谱的变化以及差异表达miRNA的病理生理特征。共鉴定出31个差异表达的miRNA,其中20个下调,11个上调。基因本体(GO)富集分析显示,差异表达miRNA的验证靶点在基因转录调控方面显著富集。京都基因与基因组百科全书分析中这些通路也显著富集,且大多数与癌症相关,包括丝裂原活化蛋白激酶信号通路、癌症相关通路、Wnt信号通路、Hippo信号通路、癌症相关蛋白聚糖和轴突导向。miRNA-基因和miRNA-GO网络分析揭示了几个关键的miRNA、基因和功能。值得注意的是,miR-3613-3p在两个网络中都起主导作用。在miRNA-基因网络中,MAP3K2、MGAT4A、TGFBR1、UBE2R2和SMAD4最有可能受改变的miRNA调控。miRNA-GO网络分析揭示了miRNA与不同功能之间存在显著复杂的关联,且差异表达miRNA显著富集的功能大多参与调控基因转录。本研究表明,miRNA参与了热处理内皮细胞的病理生理过程。了解miRNA的功能可能为内皮细胞热诱导病理生理的分子机制提供新的见解。