线粒体分裂蛋白FIS1通过诱导上皮间质转化促进肝癌侵袭与迁移

摘要

目的:研究线粒体分裂蛋白1(Mitochondrial fission protein 1,FIS1)介导的线粒体分裂对肝癌细胞侵袭与迁移的调控作用与机制.方法:采用免疫组化实验比较10对肝癌原发灶与转移灶组织中FIS1表达,以明确FIS1与肝癌转移的关系.通过siRNA干扰FIS1的表达后,用Transwell实验检测肝癌细胞迁移与侵袭能力的变化,qPCR与Western Blot检测上皮间质转化标志分子上皮型钙黏蛋白(epithelia cadherin,E-cadherin)、紧密连接蛋白(zonula occludens-1,ZO-1)、神经型钙黏蛋白(neural cadherin,N-cadherin)、波形蛋白Vimentin的表达.结果:肝癌转移灶组织中FIS1的表达显著高于原发灶组织.干扰FIS1表达后,肝癌细胞迁移和侵袭能力均明显下降,细胞上皮间质转化标志蛋白E-cadherin和ZO-1的表达上调,而N-cadherin和Vimentin的表达下调.结论:线粒体分裂蛋白FIS1在肝癌转移灶组织中高表达,并可能通过调节细胞上皮间质转化促进肝癌细胞转移.%Objective:To investigate the effects and underlying mechanisms of mitochondrial fission protein FIS1 on the migration and invasion of hepatocellular carcinoma (HCC) cells.Methods:Immunohistochemistry analysis was used for evaluating the expression levels of FIS1 in 10 cases of primary tissues and paired metastatic lesions of HCC to analyze the correlation of expression of FIS1 with the metastasis ofHCC.Transwell assays was used to detect the changes of migration and invasion capability of HCC cells after FIS1 was knocked down by RNA interference.In addition,expressions of Epithelial-Mesenchymal Transition (EMT) markers of E-cadherin,ZO-1,N-cadherin and Vimentin were detected by qPCR and Western blot after FIS1 was knocked down by RNA interference.Results:FIS1 was highly expressed in the primary tissues of HCC compared to the paired metastatic lesions.Knockdown of FIS1 inhibited the migration and invasion of HCC cells.In addition,knockdown of FIS1 repressed the expressions of epithelial markers of E-cadherin and ZO-1,while activated the expressions of mesenchymal markers of N-cadherin and Vimentin in HCC cells.Conclusions:Mitochondrial fission protein FIS1 was highly expressed in the metastatic tissues of HCC and promoted the migration and invasion of HCC cells mainly through inducing the epithelial-mesenchymal transition.