A Novel Transgenic Mouse Model Implicatesas a Promoter of Hepatocellular Carcinoma.

Abstract

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths globally. Incidence rates are steadily increasing, creating an unmet need for new therapeutic options. Recently, the inhibition of sirtuin-2 () was proposed as a potential treatment for HCC, despite contradictory findings of its role as both a tumor promoter and suppressor in vitro.functions as a lysine deacetylase enzyme. However, little is known about its biological influence, despite its implication in several age-related diseases. This study evaluated's role in HCC in vivo using an inducibletransgene inandmice.HCC mice had smaller, less proliferative, and more differentiated liver tumors, suggesting thatfunctions as a tumor promoter in this context. Furthermore,HCCs had significantly less c-MYC oncoprotein and reduction in c-MYC nuclear localization. The RNA-seq showed that only three genes were significantly dysregulated due to loss of, suggesting the underlying mechanism is due to-mediated changes in the acetylome, and that the therapeutic inhibition ofwould not perturb the oncogenic transcriptome. The findings of this study suggest thatinhibition could be a promising molecular target for slowing HCC growth.