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.