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The following is a summary of “USP54 is a potential therapeutic target in castration-resistant prostate cancer,” published in the February 2024 issue of Urology by Zhou et al.

USP54, a member of the ubiquitin-specific protease family, plays a pivotal role in the malignant evolution of various cancer types. Yet, its involvement in prostate cancer (PCa), particularly in castration-resistant prostate cancer (CRPC), remains elusive. In this study, the researchers developed the CRPC LNCaP-AI cell line derived from the hormone-sensitive prostate cancer (HSPC) LNCaP line. They conducted RNA-Seq analysis to investigate differential expression of deubiquitinases (DUBs) between LNCaP and LNCaP-AI cells. USP54 emerged as the most significantly upregulated DUB in LNCaP-AI cells compared to LNCaP cells, with elevated expression observed in PCa tissues relative to normal tissues. Subsequent knockdown experiments revealed that USP54 depletion significantly inhibited the proliferation of PCa cell lines both in vitro and in vivo. Furthermore, bioinformatics analyses unveiled potential signaling pathways modulated by USP54 in PCa, with quantitative polymerase chain reaction confirming the involvement of key pathways.

Importantly, their findings suggest a positive correlation between USP54 expression and androgen receptor (AR) signaling in PCa samples, with USP54 knockdown demonstrating a suppressive effect on AR signaling in PCa cells. In conclusion, USP54 exhibits upregulation during the transition from HSPC to CRPC, and its depletion exerts inhibitory effects on CRPC cell proliferation, potentially implicating USP54 in PCa progression through modulation of AR signaling pathways.

Source: bmcurol.biomedcentral.com/articles/10.1186/s12894-024-01418-7