EF4影响线粒体氧化磷酸化并调控膀胱癌细胞增殖及迁移

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.

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

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.