EF4影响线粒体氧化磷酸化并调控膀胱癌细胞增殖及迁移  

Aberrantly Upregulated EF4 Is Crucial for The Proliferation and Migration of Bladder Urothelial Carcinoma Cells via Orchestration of Mitochondrial Oxidative Phosphorylation

作　　者：化朝举 戴斐 邓瑶 卢俊婉 周宁宁 李琬其 张叶 黄卡特 刘永章 吕斌[2] 卫涛涛[1,4] HUA Chao-Ju;DAI Fei;DENG Yao;LU Jun-Wan;ZHOU Ning-Ning;LI Wan-Qi;ZHANG Ye;HUANG Ka-Te;LIU Yong-Zhang;Lü Bin;WEI Tao-Tao(National Laboratory of Biomacromolecules,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China;Protein Quality Control and Diseases Laboratory,Key Laboratory of Medical Genetics of Zhejiang Province,Key Laboratory of Laboratory Medicine,Ministry of Education of China,School of Laboratory Medicine and Life Sciences,Wenzhou Medical University,Wenzhou 325035,China;Yuanpei College,Peking University,Beijing 100871,China;University of Chinese Academy of Sciences,Beijing 100049,China)

机构地区：[1]中国科学院生物物理研究所生物大分子国家实验室,北京100101 [2]浙江省医学遗传学重点实验室蛋白质质量控制与疾病实验室,教育部检验医学重点实验室,温州医科大学检验医学与生命科学学院,温州325035 [3]北京大学元培学院,北京100871 [4]中国科学院大学,北京100049

出　　处：《生物化学与生物物理进展》2021年第3期317-327,共11页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金(卫涛涛,92054108,吕斌,91954101、31771534、31570772)资助项目.

摘　　要：延伸因子4(EF4)是一种非传统的线粒体延伸因子,参与调控线粒体蛋白质合成过程.在本研究中,我们进一步探索了其在膀胱癌中的作用机制.通过检测EF4在膀胱癌及邻近正常组织中的表达,发现EF4在膀胱癌患者肿瘤组织中异常升高,并在T分期较高的肿瘤中高表达.随后,通过在HTB-9和T-24膀胱癌细胞中敲低EF4的表达,进一步探索了EF4在膀胱癌发生及发展中的作用.研究结果表明,通过RNAi敲低EF4表达不仅可以抑制膀胱癌细胞HTB-9和T-24在体外的增殖和集落形成,还显著降低了其迁移能力,这一结果主要归因于下调EF4表达阻碍了线粒体DNA编码的呼吸链复合物亚基的翻译,影响呼吸链复合物的组装,并最终导致线粒体氧化磷酸化功能障碍.以上结果表明EF4通过维持线粒体重要复合物的翻译而影响膀胱癌细胞的细胞增殖迁移及膀胱癌发生发展,并提示EF4可能是治疗膀胱癌的潜在目标分子.Elongation factor 4(EF4)is a non-conventional elongation factor which regulates protein synthesis in mitochondria.In this study,we explored its function in bladder urothelial carcinoma.By analyzing the expression of EF4 in bladder urothelial carcinoma and adjacent normal tissues,we found that EF4 was aberrantly elevated in multiple cohorts of bladder cancer patients.Notably,the upregulation of EF4 was positively associated with tumor progression.By manipulating EF4 expression in HTB-9 and T-24 bladder cancer cells,the effects of upregulated EF4 was investigated.Knockdown of EF4 suppressed the proliferation and colony formation in bladder cancer cells;the ability of cells to migrate in vitro was also retarded.Knockdown of EF4 down-regulated the expression of mitochondrial DNA-encoded subunits of electron transfer chain complexes,and resulted in the dysfunction of mitochondrial oxidative phosphorylation.These results define a tumor-supportive role for EF4 by maintaining the protein synthesis within the mitochondria,which may serve as a potential therapeutic target in bladder urothelial carcinoma.

关 键 词：EF4 肿瘤发生 线粒体翻译 线粒体氧化磷酸化 膀胱癌 

分 类 号：Q291[生物学—细胞生物学] R737[医药卫生—肿瘤]