E型钙黏蛋白对胃癌AGS细胞增殖、侵袭和基因表达谱的影响  

Effect of E-cadherin on the proliferation, invasion and gene expression profile of gastric cancer AGS cells

作　　者：袁源 贾西云 李飞艳 张煊若 黄方芳 张自森[1] YUAN Yuan;JIA Xiyun;LI Feiyan;ZHANG Xuanruo;HUANG Fangfang;ZAHNG Zisen(Department of Oncology,the Fifth Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China;Department of Oncology,Nanyang Central Hospital,Nanyang 473005,China)

机构地区：[1]郑州大学第五附属医院肿瘤内科,河南郑州450052 [2]南阳市中心医院肿瘤内科,河南南阳473000

出　　处：《肿瘤基础与临床》2024年第1期1-6,共6页journal of basic and clinical oncology

基　　金：河南省医学科技攻关(省部共建)项目(201701015);河南省科技攻关计划项目(212102310618);河南省高等学校重点科研项目(22A320005)。

摘　　要：目的观察E型钙黏蛋白(E-cadherin)对胃癌AGS细胞增殖、侵袭、迁移及顺铂(DDP)化疗敏感性的影响,筛选E-cadherin可能调控的下游基因与机制。方法培养胃癌AGS细胞(对照组)和E-cadherin过表达的AGS细胞(E-cadherin过表达组)至对数生长期后,采用CCK-8方法检测2组细胞活力,采用集落形成实验检测细胞增殖能力,采用Transwell方法检测细胞侵袭和迁移能力,采用基因芯片比较分析E-cadherin过表达前后细胞基因表达谱变化,筛选差异表达基因,用生物信息学方法对差异表达基因进行基因本体(GO)注释和京都基因与基因组百科全书(KEGG)信号通路富集分析。结果与对照组比较,E-cadherin过表达组细胞活力下降更为显著(F组间=101.674,P<0.001;F组内=9.712,P=0.001;F交互=9.712,P=0.001),细胞集落数量减少(t=11.452,P<0.001),迁移和侵袭细胞数量减少(细胞迁移:t=3.994,P=0.016;细胞侵袭:t=2.971,P=0.041);在DDP作用下,与对照组比较,E-cadherin过表达组细胞活力下降更为显著(F组间=24.312,P<0.001;F组内=327.222,P<0.001;F交互=14.445,P<0.001),细胞迁移和侵袭细胞数量减少(细胞迁移:t=4.253,P=0.013;细胞侵袭:t=3.944,P=0.017);E-cadherin过表达后,共筛选出差异表达基因3882个,包括552个lncRNA、272个circRNA和3058个mRNA;GO注释显示,差异表达基因主要富集在GTP酶活性的正向调节、细胞外基质生成、血管生成等生物学过程;KEGG通路富集分析显示,差异表达基因主要富集在细胞外基质受体相互作用、丝裂原活化蛋白激酶信号通路、补体与凝血级联通路等。结论E-cadherin表达通过调节基因组变化抑制胃癌细胞增殖、迁移、侵袭,为胃癌个体化治疗策略研究提供了分子基础。Objective To investigate the effects of E-cadherin on the proliferation,invasion,migration,and cisplatin(DDP)chemotherapy sensitivity of gastric cancer AGS cells,and to screen potential downstream genes and mechanisms of E-cadherin regulation.Methods The gastric cancer AGS cells(the control group)and E-cadherin overexpressing AGS cells(the E-cadherin overexpressing group)were cultured to logarithmic growth phase.CCK-8 method was used to detect cell viability in the two groups.The colony formation assay was used to detect cell proliferation.Transwell assay was used to analyze cell invasion and migration.Genechip was used to compare and analyze the changes of cell gene expression profiles in the two groups,and to screen differentially expressed genes.Bioinformatics methods were performed for Gene Ontology(GO)annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis based on differentially expressed genes.Results Compared with the control group,the E-cadherin overexpression group showed a decrease in cell viability(between subjects effects:F=101.674,P<0.001;within subjects effects:F=9.712,P=0.001;interaction effects:F=9.712,P=0.001),a decrease in the number of cell colonies(t=11.452,P<0.001),and a decrease in the number of migratory and invasive cells(cell migration:t=3.994,P=0.016;cell invasion:t=2.971,P=0.041);under the action of DDP,compared with the control group,the E-cadherin overexpression group showed a decrease in cell viability(between subjects effects:F=24.312,P<0.001;within subjects effects:F=327.222,P<0.001;interaction effects:F=14.445,P<0.001),a decrease in the number of migratory and invasive cells(cell migration:t=4.253,P=0.013;cell invasion:t=3.944,P=0.017);there were 3882 differentially expressed genes were screened after overexpression of E-cadherin,included 552 lncRNA,272 circRNAs and 3058 mRNAs.The functions of differentially expressed genes identified were mainly involved in positive regulation of GTPase activity,extracellular matrix generation,angiogenes

关 键 词：胃癌 E型钙黏蛋白 细胞增殖 细胞侵袭 基因表达谱 

分 类 号：R735.2[医药卫生—肿瘤]