Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the world. RING finger-related E3 ubiquitin ligases play a role in tumorigenesis and can function either as oncogenes or tumor suppressors based on their target proteins. Here, we show that the expression of RNF152, a ring finger protein, in CRC tissues was significantly reduced compared with adjacent non-cancerous tissues. High expression levels of RNF152 correlated with better prognosis in patients with colorectal cancer. Low expression of RNF152 correlated with lymphatic metastasis. Overexpression of RNF152 inhibited CRC cell proliferation both in vitro and in vivo by inactivating the mechanistic target of rapamycin complex 1 (mTORC1) and inducing autophagy and apoptotic cell death. This strong inhibition was dependent on the E3 ligase activity of RNF152. Ectopic expression of the RNF152-CS-mutant, which lacks E3 ligase activity, significantly restored the proliferation ability of CRC cells. Our findings showed that RNF152 inhibits colorectal cancer growth and may be a novel prognostic biomarker for the treatment of CRC.
Keywords: Colorectal cancer; E3 ligase; RNF152; prognosis; proliferation.