Miao Changqing, Fan Dandan
Department of Emergency, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China.
Toxicol Mech Methods. 2022 Nov;32(9):678-685. doi: 10.1080/15376516.2022.2063095. Epub 2022 Jun 21.
In this study, differentially expressed genes (DEGs) and signaling pathways involved in diquat (DQ) and paraquat (PQ) poisoning were identified via bioinformatics analysis, in order to inform the development of novel clinical treatments.
Raw data from GSE153959 were downloaded from the Gene Expression Omnibus database. DEGs of the DQ vs. control (CON) and PQ vs. CON comparison groups were identified using R, and DEGs shared by the two groups were identified using TBtools. Subsequently, the shared DEGs were searched in the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, using the Database for Annotation, Visualization, and Integrated Discovery. A protein-protein interaction (PPI) network was constructed, and hub genes were identified using the cytoHubba plug-in in Cytoscape software. Finally, circos and contrast plots showing the DEGs shared between mouse and human chromosomes were constructed using TBtools.
Thirty-one DEGs shared by the DQ and PQ groups were identified. Enriched biological process terms included positive regulation of cell proliferation and translation. Enriched cellular component terms included extracellular region, intracellular membrane-bounded organelle and mitochondrion. Enriched molecular function terms included transcription factor activity and sequence-specific double-stranded DNA binding. Enriched KEGG pathways included the interleukin-17 signaling pathway, tumor necrosis factor signaling pathway, and human T-cell leukemia virus 1 infection. The top 10 hub genes in the PPI network were prostaglandin-endoperoxide synthase 2 (), chemokine (C-X-C motif) ligand 2 (), colony-stimulating factor 2 (granulocyte-macrophage) (), matrix metallopeptidase 13 (), amphiregulin (), plasminogen activator, urokinase receptor (), fos-like antigen 1 (), epiregulin (), activating transcription factor 3 (), and transferrin receptor (). and played important roles in the mitogen-activated protein kinase (MAPK) signaling pathway.
These pathways and DEGs may serve as targets for gene therapy.
本研究通过生物信息学分析鉴定出参与敌草快(DQ)和百草枯(PQ)中毒的差异表达基因(DEG)及信号通路,为新型临床治疗方法的开发提供依据。
从基因表达综合数据库下载GSE153959的原始数据。使用R软件鉴定DQ与对照组(CON)以及PQ与CON比较组的DEG,并使用TBtools鉴定两组共有的DEG。随后,利用注释、可视化和综合发现数据库在基因本体论和京都基因与基因组百科全书(KEGG)数据库中搜索共有DEG。构建蛋白质-蛋白质相互作用(PPI)网络,并使用Cytoscape软件中的cytoHubba插件鉴定枢纽基因。最后,使用TBtools构建显示小鼠和人类染色体之间共有DEG的环形图和对比图。
鉴定出DQ和PQ组共有的31个DEG。富集的生物学过程术语包括细胞增殖和翻译的正调控。富集的细胞组成术语包括细胞外区域、细胞内膜结合细胞器和线粒体。富集的分子功能术语包括转录因子活性和序列特异性双链DNA结合。富集的KEGG通路包括白细胞介素-17信号通路、肿瘤坏死因子信号通路和人类T细胞白血病病毒1感染。PPI网络中的前10个枢纽基因是前列腺素内过氧化物合酶2、趋化因子(C-X-C基序)配体2、集落刺激因子2(粒细胞-巨噬细胞)、基质金属肽酶13、双调蛋白、纤溶酶原激活剂、尿激酶受体、Fos样抗原1、表皮调节素、激活转录因子3和转铁蛋白受体。 和 在丝裂原活化蛋白激酶(MAPK)信号通路中起重要作用。
这些通路和DEG可能作为基因治疗的靶点。