In this study, we report that OTUD6A can stabilize Brg1 and AR by removing Brg1 K27-linked polyubiquitination and AR K11-linked polyubiquitination, respectively, to promote PCa progression in vitro and in vivo, suggesting that targeting OTUD6A is a reasonable strategy for PCa therapy. This evidence concerns the gene SMARCA4 and posterior cortical atrophy.