USP13 Facilitates the Proliferation of Hepatocellular Carcinoma Cells by Reducing K48/63-Linked Polyubiquitination and Degradation of PRPF6

Abstract

Ubiquitin-specific peptidase 13 (USP13) is a well-characterised deubiquitinating enzyme that plays a critical role in the pathogenesis and progression of various human malignancies. However, the precise mechanisms by which USP13 influences hepatocellular carcinoma (HCC) cell proliferation remain to be fully elucidated. In this study, we confirmed that USP13 expression was upregulated in HCC and correlated with poor prognosis. Further investigation revealed that the knockout of USP13 inhibited HCC cell proliferation, whereas overexpression of USP13 had the opposite effect. Mechanistically, pre-mRNA processing factor 6 (PRPF6) was identified as a potential substrate of USP13 through mass spectrometry analysis. USP13 stabilised the PRPF6 protein by reducing its K48/63-linked polyubiquitination levels and degradation. Ultimately, we demonstrated that the USP13-PRPF6 axis promoted HCC cell proliferation was closely associated with the activation of the AKT-mTOR signalling pathway.