RNF31 promotes proliferation and invasion of hepatocellular carcinoma via nuclear factor kappaB activation
RNF31 is a multifunctional RING finger protein involved in various inflammatory diseases and cancers. It serves as a key component of the linear ubiquitin chain assembly complex (LUBAC), which activates the nuclear factor kappaB (NF-κB) pathway by generating Met1-linked linear ubiquitin chains. This study aimed to elucidate the role of RNF31 in the pathogenesis of hepatocellular carcinoma (HCC) and its potential as a therapeutic target.
Our analysis revealed high RNF31 expression in HCC, as determined through immunohistochemistry and mRNA levels, which was associated with poorer survival outcomes in patients. In vitro experiments demonstrated that knocking down RNF31 in HCC cell lines resulted in reduced cell proliferation and invasion, as well as diminished tumor necrosis factor (TNF)-α-induced NF-κB activation. Additionally, treatment with HOIPIN-8, a specific inhibitor of LUBAC that inhibits RNF31’s ubiquitin ligase (E3) activity, produced similar effects, leading to decreased cell proliferation and invasion.
Overall, our clinical and laboratory findings indicate that RNF31 is a prognostic factor in HCC, promoting tumor aggressiveness through NF-κB activation.