TMEM117调控TGF-β信号通路促进胃癌的作用及机制研究  

Role of TMEM117 in promoting gastric cancer progression via regulating TGF-βsignaling pathway and its action mechanism

作　　者：李竞 赵梓丹 张辉 LI Jing;ZHAO Zidan;ZHANG Hui(Department of Hepatopancreatobiliary Surgery,the Third Xiangya Hospital,Central South University,Changsha 410013,China)

机构地区：[1]中南大学湘雅三医院肝胆胰外科,湖南长沙410013

出　　处：《中国普通外科杂志》2023年第9期1358-1369,共12页China Journal of General Surgery

摘　　要：背景与目的:跨膜蛋白(TMEM)是一种跨越整个脂质双分子层的蛋白质。TMEM117是TMEM家族中很重要的一员,以往研究发现TMEM117主要在调节血糖、预防心肌肥厚、参与内质网应激等方面发挥重要作用,然而TMEM117在胃癌(GC)中的作用机制尚不清楚。因此,本研究探索TMEM117在GC中的表达及其生物学功能与作用机制。方法:通过生物信息学方法分析TMEM117在泛癌中的表达情况,用qRT-PCR与Western blot检测人正常胃上皮细胞与不同GC细胞系中TMEM117 mRNA与蛋白水平的表达。用qRT-PCR检测TMEM117在GC组织与对应癌旁组织中mRNA的表达。分别在不同GC细胞系中对TMEM117进行敲低或者过表达,然后通过CCK-8实验、EdU实验、Transwell实验检测TMEM117对GC细胞功能的影响,通过Western blot检测相关通路蛋白水平以及加入相关抑制剂分析TMEM117对GC细胞产生影响的机制。最后,观察敲低TMEM117对GC细胞在裸鼠体内生长的影响。结果:数据库分析结果显示,TMEM117在多种癌症组织中表达升高,TMEM117在GC组织中的表达明显高于正常组织(P<0.05),TMEM117高表达GC患者的预后较差(P<0.05)。qRT-PCR与Western blot结果显示,GC细胞中TMEM117的mRNA与蛋白表达均明显高于正常胃上皮细胞,GC组织中的TMEM117的mRNA表达明显高于癌旁组织(均P<0.05)。细胞功能实验结果显示,敲低TMEM117的GC细胞的增殖、侵袭和迁移能力明显降低,而过表达TMEM117的GC细胞则呈反向变化(均P<0.05);敲低TMEM117的GC细胞中TGF-β的表达明显下调,而过表达TMEM117的GC细胞中TGF-β的表达明显上调;使用TGF-β抑制剂LY2157299可以部分逆转过表达TMEM117对GC细胞恶性表型的促进作用(均P<0.05)。裸鼠体内成瘤实验显示,敲低TMEM117的GC细胞在裸鼠体内的生长被明显抑制。结论:TMEM117在GC中高表达且与患者的不良预后密切相关,其促进GC进展的作用机制可能与活化TGF-β信号通路促进GC细胞的增殖及侵袭�Background and Aims:Transmembrane proteins(TMEMs)are a class of proteins that span the entire lipid bilayer.TMEM117 is an important member of the TMEM family,and previous research has shown that TMEM117 plays a significant role in regulating blood sugar,preventing myocardial hypertrophy,and participating in endoplasmic reticulum stress.However,the role of TMEM117 in gastric cancer(GC)remains unclear.Therefore,this study was conducted to explore the expression and biological functions as well as the action mechanisms of TMEM117 in GC.Methods:Bioinformatics analysis was used to assess the expressions of TMEM117 in various cancer types.qRT-PCR and Western blot were employed to measure the expression levels of TMEM117 mRNA and protein in human normal gastric epithelial cells and different GC cell lines.qRT-PCR was also used to detect TMEM117 mRNA expression in GC tissue and corresponding adjacent tissue.TMEM117 was either knocked down or overexpressed in different GC cell lines,and its effects on GC cell function were assessed using CCK-8,EdU,and Transwell assays.Western blot analysis was conducted to examine the levels of relevant pathway proteins,and the impact of TMEM117 on GC cells was analyzed by adding specific inhibitor.Finally,the effects of TMEM117 knockdown on the growth of GC cells in nude mice were observed.Results:Database analysis showed that TMEM117 was upregulated in various cancer tissues,and its expression in GC tissue was significantly higher than that in normal tissue(P<0.05).High expression of TMEM117 in GC was associated with poor prognosis(P<0.05).qRT-PCR and Western blot results revealed that TMEM117 mRNA and protein expressions in GC cells were significantly higher than those in normal gastric epithelial cells,and TMEM117 mRNA expression in GC tissue was significantly higher than that in adjacent tissue(all P<0.05).Functional experiments demonstrated that knocking down TMEM117 in GC cells significantly reduced proliferation,invasion,and migration,while overexpressing TMEM117 had the opposite

关 键 词：胃肿瘤 膜转运蛋白质类 转化生长因子Β 细胞增殖 肿瘤浸润 

分 类 号：R735.2[医药卫生—肿瘤]