The roles of E3 ligases in Hepatocellular carcinoma

Hepatocarcinogenesis is a complex multistep biological process involving genetic and epigenetic alterations that are accompanied by activation of oncoproteins and inactivation of tumor suppressors, which in turn results in Hepatocellular carcinoma (HCC), one of the common tumors with high morbidity and mortality worldwide. The ubiquitin-proteasome system (UPS) is the key to protein degradation and regulation of physiological and pathological processes, and E3 ligases are key enzymes in the UPS that contain a variety of subfamily proteins involved in the regulation of some common signal pathways in HCC. There is growing evidence that many structural or functional dysfunctions of E3 are engaged in the development and progression of HCC. Herein, we review recent research advances in HCC-associated E3 ligases, describe their structure, classification, functional roles, and discuss some mechanisms of the abnormal activation or inactivation of the HCC-associated signal pathway due to the binding of E3 to known substrates. In addition, given the success of proteasome inhibitors in the treatment of malignant cancers, we characterize the current knowledge and future prospects for targeted therapies against aberrant E3 in HCC.