Tumor cell-derived DNASE2B mediates M2 macrophage infiltration to promote prostate cancer progression through the PSA secretion.

This study sought to explore the role of DNASE2B (deoxyribonuclease II beta), a gene specifically overexpressed in prostate cancer (PCa) whose mechanism in driving disease progression remains unclear. We analyzed DNASE2B expression in the TCGA database and PCa cell lines/tissues using Western blotting, q-PCR, and immunohistochemistry. Biological functions were assessed via cell scratch, Transwell, and subcutaneous tumor assays. Immune microenvironment changes were investigated using TISCH2, GEO datasets, and Timer2.0. M2 macrophage infiltration was validated via Transwell, orthotopic models, Immunohistochemistry and immunofluorescence and flow cytometry. Downstream targets were identified, and the DNASE2B-PSA relationship was verified using q-PCR, Western blotting, and ELISA. In vivo models explored the mechanism of M2 regulation. Results showed that DNASE2B expression was significantly higher in PCa tissues than in adjacent normal tissues. Silencing DNASE2B in PC3 cells markedly inhibited malignant progression of PCa both in vitro and in vivo. DNASE2B expression was strongly positively correlated with M2 macrophage infiltration, and it indirectly promoted M2 macrophage infiltration and accelerated PCa progression by affecting PSA secretion. In summary, high DNASE2B expression in PCa cells enhances M2 macrophage infiltration by increasing PSA secretion, thereby driving malignant progression of PCa.