Abstract
Background: Castration-resistant prostate cancer (CRPC) represents the terminal stage of prostate cancer (PCa), yet the molecular mechanisms driving its development remain unclear. Members of the histone lysine demethylase (KDM) family regulate histone methylation and thereby modulate transcriptional programs during malignant progression, contributing to PCa pathogenesis. While the function of KDM3B in PCa has been described, its involvement in CRPC remains uncertain. This study investigated the mechanistic role of KDM3B in CRPC progression. Methods: Clinical specimens and publicly available datasets were analyzed to assess KDM3B expression in PCa and CRPC tissues. Cellular proliferation was evaluated through CCK-8 and colony formation assays. In addition, RT-PCR, WB, and CCK-8 assays were employed to elucidate the relationship between KDM3B activity and CRPC development. Results: KDM3B expression was markedly reduced in both PCa and CRPC samples. Functional assays indicated that KDM3B suppressed the proliferative capacity of CRPC cells in vivo. Moreover, KDM3B upregulated PTEN expression, and its regulatory effect on CRPC cell proliferation was mediated through PTEN modulation. Conclusion: The findings suggest that KDM3B suppresses CRPC cell proliferation by enhancing PTEN expression, highlighting its potential role as a tumor-suppressive factor in PCa.