Spindle pole body component 25 in the androgen-induced regression of castration-resistant prostate cancer.

Background: Androgen plays a critical role in the development and growth of prostate cancer (PCa) by binding to the androgen receptor, a steroid receptor for testosterone and dihydrotestosterone (DHT). Androgen deprivation therapy, a clinical endocrine therapy, has resulted in increases in the occurrence of castration-resistant prostate cancer (CRPC); however, the mechanisms of CRPC have not yet fully been determined. We previously showed that spindle pole body component 25 (SPC25), a component of the NDC80 complex that is critical in kinetochore formation and chromosome segregation during the cell cycle, plays a critical role in PCa tumorigenesis and cancer stemness. However, it is not yet known whether SPC25 plays a role in CRPC; thus, we sought to address this question in the current study. Methods: SPC25 levels were detected in androgen-insensitive PCa cells using the public database and bioinformatics tools. In vitro, SPC25 levels were determined in androgen-sensitive and androgen-insensitive PCa cells treated with or without DHT. The growth of the PCa cells was assessed by the Cell Counting Kit-8 assay. The invasiveness and migratory potential of the PCa cells were assessed by the transwell cell invasive assay and migratory assay, respectively. Gain-of-function and loss-of-function experiments examined the transfection of androgen-sensitive and androgen-insensitive PCa cells by plasmids carrying small-interfering ribonucleic acids for SPC25 or SPC25, respectively. Results: SPC25 levels were significantly reduced in the androgen-insensitive PCa cells treated with DHT in the Public database. In vitro, PCa cell growth, invasion, and metastasis was reduced in androgen-insensitive PCa cells but increased in androgen-sensitive PCa cells treated with DHT, partially through DHT-regulated expression of SPC25 at transcriptional but not at translational levels. Conclusions: Androgen treatment reduces CRPC growth, invasion, and metastasis partially through its regulation of SPC25. SPC25 represents a promising target in the treatment of CRPC.