The role of abnormal ubiquitination in hepatocellular carcinoma pathology

Primary liver cancer is known for its high incidence and fatality rate. Over the years, therapeutic strategies for primary liver cancer have advanced significantly. Nonetheless, a substantial number of patients have not benefited from these methods, underscoring the pressing need for new and effective treatments for primary liver cancer. Ubiquitination is a critical post-translational modification that enables proteins to fulfill their normal biological functions and maintain their expression stability within cells. Importantly, increasing evidence suggests that the progression of liver cancer cells is often accompanied by disruptions in protein ubiquitination and deubiquitination processes. In this comprehensive review, we have compiled pertinent research about dysregulated ubiquitination in hepatocellular carcinoma (HCC) to broaden our understanding in this field. We elucidate the connections between the ubiquitination proteasome system, deubiquitination, and HCC. Furthermore, we shed light on the role of ubiquitination in cells situated within the tumor microenvironment of HCC including its involvement in mediating the activation of oncogenic pathways, reprogramming metabolic processes, and perturbing normal cellular functions. In conclusion, targeting the dysregulation of ubiquitination in HCC holds promise as a prospective and complementary therapeutic approach to existing treatments.