RNF128 suppresses the malignancy of colorectal cancer cells via inhibition of Wnt/β-catenin signaling

Am J Transl Res. 2021 Dec 15;13(12):13567-13578. eCollection 2021.

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: Our research demonstrated that RNF128 inhibited cell proliferation and metastasis of CRC cells via Wnt/β-catenin signaling-mediated deubiquitination.

Keywords: RNF128; Wnt/β-catenin signaling; colorectal cancer; ubiquitination.