Neuroendocrine prostate cancer (NEPC)-associated promotes cisplatin resistance in prostate cancer by regulating CDK1 phosphorylation.

Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of castration-resistant prostate cancer (CRPC) that is typically resistant to nearly all current therapies. In this study, single-cell RNA sequencing (scRNA-seq) and dataset analyses identified Centrosomal Protein 55 () as a critical factor in the transformation from hormone-sensitive prostate cancer (HSPC) to CRPC and, ultimately to, NEPC. Subsequent bioinformatics analyses and validation with clinical samples demonstrated that is significantly upregulated in NEPC tissues compared to HSPC and CRPC. Furthermore, while show no significant association with the immune microenvironment or cancer-associated fibroblasts (CAFs), our findings indicate that it directly mediates the plasticity of prostate cancer cells, thereby driving NEPC progression. Specifically, and experiments confirmed that enhances cell proliferation, migration, invasion and the expression of NEPC biomarkers in prostate cancer. Importantly, although cisplatin is the primary treatment for NEPC clinically, has been shown to regulate cisplatin resistance through the phosphorylation of CDK1 at the tyrosine 15 (Tyr15) site. In summary, our study identifies a key gene that influences the neuroendocrine differentiation process in prostate cancer, suggesting its potential as an important therapeutic target.