大鼠肝脏再生终止阶段差异基因表达的生物信息学分析  

Bioinformatics analysis of differential gene expression of termination phase of liver regeneration in rats

作　　者：刘一鸣[1] 袁方超[1] 王孟皓 LIU Yiming;YUAN Fangchao;WANG Menghao(Department of Hepatobiliary Surgery,Second Affiliated Hospital of Chongqing Meidical University,Chongqing 400010,China)

机构地区：[1]重庆医科大学附属第二医院肝胆外科,重庆400010

出　　处：《检验医学与临床》2020年第7期921-925,929,共6页Laboratory Medicine and Clinic

摘　　要：目的通过生物信息学方法分析参与肝脏再生(LR)终止阶段调控的相关基因,以探讨该阶段精确调控肝脏大小所涉及的相关分子机制。方法从美国国立生物技术信息中心(NCBI)的高通量基因表达数据库(GEO)下载大鼠部分肝脏切除(PH)术后肝组织基因表达数据集(GSE63742),选取LR终止阶段样本(PH术后7 d)并使用R语言筛选出该阶段所有差异表达基因(DEGs)。利用在线功能富集数据库DAVID对DEGs进行富集分析。利用线上蛋白质相互作用检索数据库(STRING数据库)构建DEGs的蛋白质-蛋白质互作用网络(PPI网络)并使用Cytoscape软件筛选该网络中的关键节点及关键基因。结果共筛选出136个有统计学意义的DEGs,其中包括70个上调基因及66个下调基因。京都基因与基因组百科全书(KEGG)通路富集分析提示DEGs主要与类固醇激素合成、维生素A代谢、丝裂原活化蛋白激酶(MAPK)信号通路、转化生长因子-β(TGF-β)通路等密切相关。基因本体富集表明DEGs主要与Notch信号通路负向调控、环氧酶P450通路、细胞外区域、外泌体、芳香酶活性以及类固醇羟化酶活性等过程、组分以及功能相关。STRING数据库和Cytoscape软件分析发现Cyp2c13、ste2、Mup5、LOC259244、Rup2、Hsd3b5、UST4r、Btg2、Cyp2c11、Myc为调控LR终止阶段的关键基因。结论采用生物信息学方法筛选出LR终止阶段DEGs中包含ste2、Btg2等关键基因,上述基因可能参与大鼠LR终止阶段调控,其调控机制与MAPK、TGF-β等通路相关。Objective To reveal the underlying molecular mechanisms involved in the regulation of liver size during the termination phase of liver regeneration(LR)by bioinformatics methods and relative genes were analyzed.Methods Gene datasets(GSE63742)of rat liver tissue after partial hepatectomy(PH)was downloaded from the Gene Expression Omnibus(GEO)of the National Center for Biotechnology Information(NCBI),and samples of late stage LR(7 days after PH)were selected and screened by R language to identify differentially expressed genes(DEGs).An online database for annotation visualization and integrated discovery(DAVID)were then used to conduct enrichment analysis.Protein-protein interaction(PPI)networks of DEGs were constructed by the Search Tool for the Retrieval of Interacting proteins(STRING)database and hub nodes and genes were predicted by Cytoscape software.Results A total of 136 statistically significant DEGs were screened including 70 up-regulated and 66 down-regulated genes.Kyoto Encyclopedia of genes and Genomes(KEGG)pathway enrichment analysis suggested that DEGs mainly related to pathways including steroid hormone synthesis,retinol metabolism,mitogen-activated protein kinase(MAPK)signaling and transforming growth factor-β(TGF-β).GO enrichment indicated that DEGs were mainly involved in negative regulation of Notch signaling pathway,cyclooxygenase P450 pathway,extracellular domain,exosomes,aromatase activity,and steroid hydroxylase activity.The STRING database and Cytoscape software analysis found that Cyp2c13,ste2,Mup5,LOC259244,Rup2,Hsd3b5,UST4r,Btg2,Cyp2c11 and Myc were hub genes in the termination phase of LR.Conclusion DEGs including ste2 and Btg2 are screened by bioinformatics methods.These genes may be involved in regulating the termination phase of LR in rats,and the underlying mechanisms may contain MAPK and TGF-βsignaling pathways.

关 键 词：肝脏再生 差异表达基因 富集分析 蛋白质互作用网络 

分 类 号：R656[医药卫生—外科学]