USP7 deubiquitinates Aurora B and promotes hepatocellular carcinoma progression

The importance of the deubiquitinase ubiquitin-specific peptidase 7 (USP7) in the etiology of various cancers is well recognized; however, its specific role and mechanisms of action in hepatocellular carcinoma (HCC) remain insufficiently elucidated. Aurora kinase B (Aurora B) has been implicated in HCC progression, yet the regulation of its protein stability in this setting is poorly defined. Here, we report that USP7 directly interacts with Aurora B, stabilizing the kinase by preventing its ubiquitination and subsequent degradation. Silencing USP7 increases the ubiquitination and degradation of Aurora B, concomitant with a reduction in HCC cell proliferation, wound healing, and migratory capacities. Conversely, USP7 overexpression enhances these malignant phenotypes, which are reversed by Aurora B knockdown. Importantly, dual inhibition of USP7 and Aurora B in vivo has marked therapeutic efficacy against HCC. Moreover, high expression of the USP7-Aurora B axis is correlated with adverse outcomes in HCC patients and may serve as an independent prognostic indicator. Collectively, our findings identify a previously unrecognized substrate relationship between USP7 and Aurora B, underscoring the pivotal role of the USP7-Aurora B axis in HCC progression. These findings offer promising avenues for therapeutic intervention and prognostication in HCC.