Deubiquitination in prostate cancer progression: role of USP22

Prostate cancer (PCa) is the leading cause of cancer death in men. With more therapeutic modalities available, the overall survival in PCa has increased significantly in recent years. Patients with relapses after advanced secondgeneration anti-androgen therapy however, often show poor disease prognosis. This group of patients often die from cancer-related complicacies. Multiple approaches have been taken to understand disease recurrence and to correlate the gene expression profile. In one such study, an 11-gene signature was identified to be associated with PCa recurrence and poor survival. Amongst them, a specific deubiquitinase called ubiquitin-specific peptidase 22 (USP22) was selectively and progressively overexpressed with PCa progression. Subsequently, it was shown to regulate androgen receptors and Myc, the two most important regulators of PCa progression. Furthermore, USP22 has been shown to be associated with the development of therapy resistant PCa. Inhibiting USP22 was also found to be therapeutically advantageous, especially in clinically challenging and advanced PCa. This review provides an update of USP22 related functions and challenges associated with PCa research and explains why targeting this axis is beneficial for PCa relapse cases.