KDM6A suppresses proliferation and epithelial-mesenchymal transition in prostate cancer cells.

BACKGROUND AND OBJECTIVE: Prostate cancer is one of the most common male malignancies worldwide. KDM6A, a histone H3K27 demethylase, has been implicated in various cancers; however, its specific functions in prostate cancer remain controversial. This study aimed to investigate the regulatory role of KDM6A in castration-resistant prostate cancer (CRPC). METHODS: We analyzed the GEO public database and conducted in vitro and in vivo experiments to examine the function of KDM6A in CRPC. RESULTS: KDM6A expression was downregulated in CRPC compared with primary prostate cancer. KDM6A acted as a tumor suppressor; its depletion promoted proliferation and migration of prostate cancer cells both in vitro and in vivo. Suppression of KDM6A activated epithelial-mesenchymal transition (EMT) via HMGB2, thereby regulating the invasive behavior of prostate cancer. EMT is known to play a critical role in CRPC progression. CONCLUSIONS: Our findings reveal the functional role of KDM6A in CRPC and suggest its potential utility in exploring novel therapeutic strategies for CRPC.