Zhu Yue, Gan Yujie, Zou Renrui, Sha Huanhuan, Lu Ya, Zhang Yuan, Feng Jifeng
The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research Nanjing 210009, Jiangsu, China.
Nanjing Jinling Hospital Nanjing 210002, Jiangsu, China.
Am J Transl Res. 2021 Dec 15;13(12):13567-13578. eCollection 2021.
Colorectal cancer (CRC) is one of the most frequent tumors and causes of mortality worldwide. Ubiquitin ligase was reported to regulate multiple cellular processes, including tumorigenesis. As ubiquitin E3 ligases, RING-finger proteins play a key role in physiological and pathophysiological processes.
We compared the expression levels of RNF128 in CRC tissues by western-blotting and qRT-PCR. Knockdown and overexpression of RNF128 were performed to examine its effect on proliferation and metastasis of CRC cells. Using western blot and co-immunoprecipitation assays, we explored the possible mechanisms underlying the effect of RNF128 in CRC cells.
We found that the expression level of RNF128 was correlated with the CRC tumorigenicity. Overexpression or knockdown of RNF128 suppressed or elevated CRC cell proliferation, migration and invasion, respectively. We further determined that RNF128 regulated β-catenin ubiquitination and thus inhibited Wnt/β-catenin signaling in CRC cells.
Our research demonstrated that RNF128 inhibited cell proliferation and metastasis of CRC cells via Wnt/β-catenin signaling-mediated deubiquitination.
结直肠癌（CRC）是全球最常见的肿瘤之一，也是主要的致死原因。据报道，泛素连接酶可调节多种细胞过程，包括肿瘤发生。作为泛素E3连接酶，环指蛋白在生理和病理生理过程中起关键作用。
我们通过蛋白质免疫印迹法和定量逆转录聚合酶链反应（qRT-PCR）比较了RNF128在结直肠癌组织中的表达水平。通过敲低和过表达RNF128来检测其对结直肠癌细胞增殖和转移的影响。利用蛋白质免疫印迹法和免疫共沉淀试验，我们探究了RNF128在结直肠癌细胞中发挥作用的潜在机制。
我们发现RNF128的表达水平与结直肠癌的致瘤性相关。RNF128的过表达或敲低分别抑制或促进了结直肠癌细胞的增殖、迁移和侵袭。我们进一步确定RNF128调节β-连环蛋白的泛素化，从而抑制结直肠癌细胞中的Wnt/β-连环蛋白信号通路。
我们的研究表明，RNF128通过Wnt/β-连环蛋白信号通路介导的去泛素化作用抑制结直肠癌细胞的增殖和转移。
