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生物信息学分析沉默HIF-1α后胃腺癌细胞系基因表达变化同胃腺癌发生发展的相关性研究 预览

Using bioinformatics analysis to identification the association between differentially expressed genes and the development of gastric adenocarcinoma by knockdown hypoxia induced factor-1 α in gastric adenocarcinoma cell
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摘要 目的:探寻缺氧诱导因子-1α(hypoxia induced factor-1α,HIF-1α)在表达和敲除的情况下胃腺癌细胞系中的基因表达特点,并揭示差异表达基因(differentially expressed genes,DEGs)的相互作用。方法:从GEO数据库中下载基因表达谱数据GSE57200, 共包括9个样本细胞株:4株导入空白对照的胃腺癌AGS细胞系和5株经慢病毒处理沉默HIF-1α的AGS细胞系。对DEGs的富集分析采用了GO(gene ontology)和KEGG(kyoto encyclopedia of genes and genomes)数据库数据,蛋白-蛋白相互作用(protein-protein interaction,PPI)网络由Cytoscpe软件实现。结果:共筛选出DEGs 510个,GO主要富集在有机物反应、蛋白质代谢、细胞信号传导和细胞通信等,KEGG通路主要富集在谷胱甘肽代谢和细胞色素P450参与外来化合物代谢等。MAPK3(mitogen-activated protein kinase 3,MAPK3又名extracellular regulated protein kinase 1,ERK1)是PPI得到的排名最高的基因节点。MCODE模型显示DEGs主要与JAK/STAT传导通路、MEK/ERK传导通路相关,两者均与恶性肿瘤的侵袭转移密切相关。在胃腺癌细胞中HIF-1α和MAPK3均呈过表达,通过感染慢病毒下调HIF-1α的表达后,MAPK3的表达也随之下调,两者正相关。结论:本研究在一定程度上揭示了在HIF-1α诱导下胃腺癌的发生发展,可能为后续胃腺癌相关的诊断和治疗提供有价值的分子靶标。 Objective:The aim of this study was to identify gene signatures during GA with or without the expression of HIF-1α and uncover their potential mechanisms.Methods:The gene expression profiles of GSE57200 were downloaded from GEO database.It contained 9 samples,including 4 untreated AGS cells and 5 HIF-1α-deficient AGS cells.The genes ontology(GO) and kyoto encyclopedia of genes and genomes pathway(KEGG) enrichment analyses were performed,and protein-protein interaction(PPI) network of the differentially expressed genes(DEGs) was constructed by cytoscape software.Results:In total,510 DEGs were identified in GA.GO analysis results showed DEGs were significantly enriched in response to organic substance,regulation of protein metabolic process,regulation of signal transduction,regulation of cell communication and so on.KEGG pathway analysis showed the DEGs were enriched in glutathione metabolism,metabolism of xenobiotics by cytochrome P450 and so on.MAPK3(mitogen-activated protein kinase 3,extracellular regulated protein kinase 1,ERK1) was the highest degree node dentified from the PPI network,and sub-networks revealed these genes were involved in significant pathways,including JAK/STAT signaling pathway and MEK/ERK signaling pathway which have a close connection with invasion and metastasis of cancer.HIF-1α and MAPK3 were overexpression in GA cells.After infected HIF-1α-shRNA into GA cells the MAPK3 level were downregulated.Conclusion:The present study indicated that the identified DEGs and hub genes promote our understanding of the molecular mechanisms underlying the development of GA induced by HIF-1α,and might be used as molecular targets and diagnostic biomarkers for the treatment of GA.
作者 张峻 武月 赵岩 王跃 郑志超 Zhang Jun1 , Wu Yue2, Zhao Yan1 , Wang Yue1 ,Zheng Zhichao1( 1 Gastric Surgery Ward ,Liaoning Cancer Hospital & Institute, China Medical University,Liaoning Shenyang 110042, China ;2 Department of Emergency,Sheng~ing Hospital, China Medical University,Liaoning Shenyang 110004, China.)
出处 《现代肿瘤医学》 CAS 2018年第8期1155-1162,共8页 Journal of Modern Oncology
基金 辽宁省自然科学基金(编号:2015020269)
关键词 胃腺癌 缺氧诱导因子-1Α 生物信息学 高通量测序 gastric adenocarcinoma, hypoxia induced factor - 1 α, bioinformatics, next generation sequencing
作者简介 张峻(1986-),男,辽宁沈阳人,医师,主要从事消化道肿瘤侵袭转移的机制研究。E—mail:surgeonzhangjun@hotmml.com;【通讯作者】郑志超(1964-),男,辽宁沈阳人,博士,主任医师,主要从事胃肿瘤发生发展的机制研究。E-mail:drzhengzhichao@126.com
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