Our results illustrated that HMGB1 exerts these functions through constitutively activating the PI3K/Akt signaling pathway, modulating the expression of Brahma-related gene 1 (BRG1, also known as SMARCA4) in PCa cells, and regulating EMT via BRG1. Thus, our study has revealed a potential mechanism by which HMGB1 mediates the development and progression of PCa. Here, AKT1 is linked to posterior cortical atrophy.