SMRACAD1通过上皮-间充质转化促进胃癌细胞生长和迁移的机制研究  

Mechanism of epithelial-mesenchymal transition-mediated promotion of gastric cancer cell growth and metastasis by SMRACAD1

作　　者：田小容 刘嘉玺 占婷 陈梦阁 田霞[2] 黄晓东 TIAN Xiaorong;LIU Jiaxi;ZHAN Ting;CHEN Mengge;TIAN Xia;HUANG Xiaodong(Department of Gastroenterology,Zhongnan Hospital of Wuhan University,Wuhan 430071,China;Department of Gastroenterology,Wuhan Third Hospital(Tongren Hospital of Wuhan University),Wuhan 430060,China)

机构地区：[1]武汉大学中南医院消化内科,武汉430071 [2]武汉市第三医院(武汉大学附属同仁医院)消化内科,武汉430060

出　　处：《数理医药学杂志》2024年第1期34-40,共7页Journal of Mathematical Medicine

基　　金：湖北省中央引导地方科技发展专项(2019ZYYD067);武汉市2022年度知识创新专项曙光计划项目(2022020801020552)。

摘　　要：目的探讨SMRACAD1对胃癌细胞增殖和侵袭的影响及作用机制。方法对癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库中373个胃癌组织和32个正常组织的SMRACAD1表达进行差异分析及京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析,采用蛋白印迹法(Western blot,WB)和实时荧光定量聚合酶链反应(quantitative real-time polymerase chain reaction,qPCR)检测SMRACAD1在人正常胃黏膜上皮细胞(GES-1)、人胃癌细胞(HGC-27)和人胃腺癌细胞(AGS)的表达。构建AGS细胞下调SMRACAD1表达和空白对照模型,平板克隆和CCK-8实验检测AGS细胞的增殖能力,划痕实验检测迁移能力,Transwell实验检测迁移和侵袭能力。WB检测SMRACAD1下调后对上皮-间充质转化(epithelial-mesenchymal transition,EMT)相关蛋白表达(E-cadherin、N-cadherin、Vimentin、Snail)及PI3K/AKT/mTOR信号通路的影响。结果SMRACAD1在胃癌组织和AGS细胞中高表达。下调SMRACAD1表达抑制了AGS细胞增殖、侵袭和迁移能力(P<0.05),抑制了AGS细胞EMT过程和PI3K/AKT/mTOR信号通路的激活。结论SMARCDA1在胃癌组织和胃癌细胞系中表达上调,通过抑制PI3K/AKT/mTOR信号通路激活下调SMRACAD1表达可抑制胃癌细胞的增殖、侵袭、迁移和EMT。Objective To investigate the effects of SMRACAD1 on gastric cancer cell proliferation and invasion and its mechanism.Methods Differential analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis of SMRACAD1 expression from 373 gastric cancer tissues and 32 normal tissues in The Cancer Genome Atlas(TCGA)database were performed;SMRACAD1 expression in human normal gastric mucosal epithelial cells(GES-1),human gastric cancer cells(HGC-27)and human gastric adenocarcinoma cells(AGS)was detected by protein blotting(Western blot,WB)and quantitative real-time polymerase chain reaction(qPCR).The model of down-regulated SMRACAD1 expression by AGS cells and a blank control model were constructed.The down-regulated SMRACAD1 expression and blank control model of AGS cells were constructed,and the proliferation ability of AGS cells was detected by plate cloning and CCK-8 assay,the migration ability was detected by scratch assay,and the migration and invasion ability were detected by Transwell assay.The effects of SMRACAD1 down-regulation on the expression of epithelial-mesenchymal transition(EMT)-related proteins(E-cadherin,N-cadherin,Vimentin,Snail)and PI3K/AKT/mTOR signaling pathways were detected by WB.Results SMRACAD1 was highly expressed in gastric cancer tissues and AGS cells.Down-regulating the SMRACAD1 expression inhibited the proliferation,invasion and migration ability of AGS cells(P<0.05),and inhibited the activation of EMT process and PI3K/AKT/mTOR signaling pathways in AGS cells.Conclusion SMARCDA1 is upregulated in gastric cancer tissues and cell lines,and the downregulation of SMRACAD1 expression by inhibiting activation of the PI3K/AKT/mTOR signaling pathways can inhibit gastric cancer cell proliferation,invasion,migration,and EMT.

关 键 词：SMARCAD1 胃癌 上皮-间充质转化 PI3K/AKT/mTOR信号通路 

分 类 号：R735.2[医药卫生—肿瘤]