MARCH5通过诱导上皮间质转化促进肝癌细胞转移  

MARCH5 promotes metastasis of liver cancer cells by inducing epithelial-mesenchymal transition

作　　者：耿西林[1] 李仙莉 李晖[1] 张煜[1] 常虎林[1] GENG Xi-lin;LI Xian-li;LI Hui;ZHANG Yu;CHANG Hu-lin(Department of Hepatobiliary Surgery,Shaanxi Provincial People’s Hospital,Xi’an 710032,China)

机构地区：[1]陕西省人民医院肝胆外科,陕西西安710068

出　　处：《肝胆胰外科杂志》2020年第12期737-742,753,共7页Journal of Hepatopancreatobiliary Surgery

基　　金：陕西省自然科学基金青年项目(2020JQ-948)。

摘　　要：目的探讨线粒体E3泛素蛋白连接酶MARCH5[membrane-associated ring finger(C3HC4)5]在肝癌转移中的调控作用。方法(1)采用生物信息学方法分析TCGA库中肝癌细胞中MARCH5表达是否发生了异常改变,并进一步分析MARCH5表达与肝癌患者预后相关性。(2)采用细胞生物学方法下调人肝癌细胞HLE中MARCH5表达后,利用划痕实验与Transwell侵袭实验分析对细胞迁移与侵袭能力的影响;下调人肝癌细胞HLE中MARCH5表达后,利用qRT-PCR实验分析对上皮间质转化标志分子(上皮标志Ecadherin与ZO-1;间质标志N-cadherin与Vimentin)表达的影响。结果(1)与正常肝组织相比,肝癌组织中MARCH5表达显著上调(P<0.001),尤其在转移性肝癌组织中(P<0.001);MARCH5高表达与患者不良预后显著相关(P=0.027)。(2)下调MARCH5表达可显著抑制人肝癌细胞HLE的迁移与侵袭能力;下调MARCH5表达后HLE细胞中上皮细胞标志分子E-cadherin与ZO-1表达显著上调,而间质细胞标志分子Ncadherin与Vimentin表达显著下调(P<0.05)。结论MARCH5表达上调可能通过诱导上皮间质转化促进肝癌细胞的迁移与侵袭。Objective To explore the biological functions of membrane-associated ring finger(C3HC4)5(MARCH5)in metastasis of liver cancer.Methods(1)Bioinformatic analysis was applied to evaluate the expression of MARCH5 in liver cancer,as well as its prognostic significance for patients with liver cancer.(2)Effects of MARCH5 knockdown on migration and invasion abilities of liver cancer cells were determined by wound healing and transwell invasion assays in HLE cells.Effects of MARCH5 knockdown on the expressions of epithelial-mesenchymal transition markers(epithelial cell markers E-cadherin and ZO-1;mesenchymal cell markers N-cadherin and Vimentin)were determined by qRT-PCR analysis in HLE cells.Results(1)MARCH5 expression was significantly increased in tissues of liver cancer when compared with that in normal liver(P<0.001),especially in tumor tissues with metastasis to lymph nodes(P<0.001).MARCH5 over-expression was significantly associated with poor survival of patients with liver cancer.MARCH5 knockdown significantly suppressed both migration and invasion abilities of HLE cells(P=0.027).(2)MARCH5 knockdown significantly increased the expressions of epithelial cell markers E-cadherin and ZO-1,while suppressed the expressions of mesenchymal cell markers of N-cadherin and Vimentin(all P<0.05).Conclusion Up-regulation of MARCH5 may promote the migration and invasion of liver cancer cells by inducing epithelial-mesenchymal transition.

关 键 词：膜相关锌指蛋白5 线粒体 迁移 侵袭 肝癌 

分 类 号：R735.7[医药卫生—肿瘤]