Abstract
Liver cancer is one of the most common malignant tumours in humans, and a large proportion of patients are diagnosed at an advanced stage due to rapid growth and distant metastasis; thus, there is an urgent need to identify critical genes involved in the development of liver cancer. In this study, we investigated the role of RING finger protein 157 (RNF157) in liver cancer proliferation and the related mechanisms. First, we used bioinformatics counting for database mining of RNF157 expression in hepatocellular carcinoma and paracancerous tissues and its relationship with prognosis. We detected the expression level of RNF157 in human samples and different liver cancer cell lines via fluorescence quantitative polymerase chain reaction (Q-PCR), Western blot, and immunohistochemistry (IHC). Subsequently, virus transfection was used to construct knockdown and overexpressed stably transfected cell lines to test the effect of RNF157 on the proliferation of liver cancer. Immunoprecipitation (Co-IP) was used to verify the binding and regulatory relationship between RNF157 and RIG-I/DDX58. We found that RNF157 expression was significantly upregulated in liver cancer tissues and correlated with poor prognosis. In addition, knockdown of RNF157 expression inhibited liver cancer cell proliferation and overexpression of RNF157 promoted liver cancer cell proliferation. Co-IP results revealed that RNF157 binds to and downregulates the expression level of RIG-I/DDX58, further suggesting that RNF157 binds to and ubiquitinates RIG-I/DDX58 at residue 48 of the lysine, which leads to a significant increase in the expression level of RIG-I/DDX58. In this study, we found that RNF157 is a tumour-promoting ubiquitin ligase that promotes liver cancer growth by targeting RIG-I/DDX58 for degradation. Thus, RNF157 has the potential to be a therapeutic target for liver cancer.
Keywords:
E3 ubiquitin ligases; Hepatocellular carcinoma; RIG-I/DDX58; RNF157; Ubiquitination.