ANKRD1通过介导上皮细胞间充质转化促进肝细胞肝癌增殖与转移  

ANKRD1 promotes proliferation and metastasis of hepatocellular carcinoma by activating epithelial mesenchymal transition pathway

作　　者：朱德明 孔连宝 贾文博 夏金国 ZHU Deming;KONG Lianbao;JIA Wenbo;XIA Jinguo(Hepatobiliary Centre,the First Affiliated Hospital of Nanjing Medical University,Key Laboratory of Liver Transplantation,Chinese Academy of Medical Sciences,National Health Commission(NHC)Key Laboratory of Living Donor Liver Transplantation,Nanjing 210029,China)

机构地区：[1]南京医科大学第一附属医院肝胆中心,中国医学科学院肝移植重点实验室,国家卫生健康委员会活体供肝移植重点实验室,江苏南京210029

出　　处：《南京医科大学学报（自然科学版）》2023年第4期484-491,共8页Journal of Nanjing Medical University(Natural Sciences)

基　　金：国家自然科学基金(81871260)。

摘　　要：目的:探究ANKRD1在肝细胞肝癌(hepatocellular carcinoma,HCC)中的表达情况,研究ANKRD1促进HCC细胞增殖和转移的功能及其机制。方法:通过实时定量RT⁃PCR(real⁃time quantitative PCR,RT⁃qPCR)与Western blot检测ANKRD1在肝细胞肝癌及癌旁组织中的相对表达量,临床病理学分析ANKRD1表达与HCC患者临床特征的相关性。利用慢病毒感染将肝癌细胞系中的ANKRD1敲低或过表达,通过CCK⁃8、划痕、Transwell、EdU以及裸鼠皮下成瘤实验在体内体外检测ANKRD1对肝癌细胞增殖与迁移功能的影响。Western blot技术检测ANKRD1对HCC细胞上皮细胞⁃间充质转化(epithelial⁃mesenchymal transition,EMT)的调控作用。结果:ANKRD1在肝癌细胞中表达明显上调,过表达ANKRD1可以促进肝癌细胞增殖、迁移、侵袭,而ANKRD1敲低则会抑制肝癌细胞的增殖与迁移,Western blot与皮下瘤免疫组化实验表明ANKRD1可以促进HCC细胞EMT通路激活。结论:ANKRD1在肝癌细胞中表达上调并通过调控EMT通路促进HCC细胞增殖与迁移,有望成为肝癌治疗的新靶点。Objective:This study aims to explore the expression of ANKRD1 in hepatocellular carcinoma(HCC)and investigate the function and mechanism of ANKRD1 in promoting the proliferation and metastasis of HCC.Methods:The relative expression of ANKRD1 in hepatocellular carcinoma and adjacent tissues was detected by RT⁃qPCR and Western blot.Clinicopathological analysis was used to assess the association of ANKRD1 with the clinical feature of HCC patients.ANKRD1 was knocked down or overexpressed in HCC cell lines by lentiviral infection.The effects of ANKRD1 on the proliferation and migration of HCC cells were detected by CCK⁃8 assay,wound healing assay,transwell assay,EdU assay in vitro and subcutaneous tumor model in vivo.The activity of epithelial⁃mesenchymal transition(EMT)pathway was examined by Western blot.Results:ANKRD1 was upregulated in HCC.Overexpression of ANKRD1 promoted the proliferation,migration and invasion of HCC cells,while knockdown of ANKRD1 inhibited the proliferation and migration of HCC cells.Western blot and immunohisbochemical assay of subcutaneous tumor showed that ANKRD1 could activate EMT pathway.Conclusion:ANKRD1 is upregulated in HCC and promotes the proliferation and migration of HCC cells by regulating the EMT pathway,providing a potential therapeutic target for HCC.

关 键 词：ANKRD1 肝细胞肝癌 上皮细胞⁃间充质转化 

分 类 号：R735.7[医药卫生—肿瘤]