APOBEC3B-driven mutations negatively regulated by P53 promote tumor progression and immunosuppressive microenvironment in prostate cancer.

APOBEC3B (A3B), a key cytosine deaminase, plays a multifaceted role in the malignant progression of various cancers. However, the precise role of A3B in prostate cancer (PCa) remains largely elusive. This study aimed to investigate the functional significance of A3B in PCa and evaluate its potential as a therapeutic target. We first demonstrated that A3B is significant upregulated in PCa tissues and positively correlated with higher Gleason scores, poorer prognostic outcomes, and an increased frequency of cytosine deamination-induced mutagenesis. Functional enrichment analysis further revealed that A3B is closely associated with biological processes such as "cell cycle regulation" and "epithelial-mesenchymal transition (EMT)." To validate the biological role of A3B in PCa cells, we conducted a series of in vitro assays, including CCK-8, EdU, colony formation, and transwell migration/invasion. Notably, A3B knockdown suppressed the proliferation of PC-3 cells and reduced their migratory and invasive capabilities by modulating EMT. Conversely, A3B overexpression enhanced these effects in 22RV1 cells. In vivo tumor xenograft experiments further supported our findings, confirming that A3B promotes the growth of PCa cells in mice. Mechanistically, p53 was identified as a suppressor of A3B expression, thereby alleviating genomic instability. Additionally, a combination of multiplex immunofluorescence (mfIHC) and qRT-PCR analyses validated that elevated A3B expression correlates with increased infiltration of immunosuppressive cells, including regulatory T cells (Tregs), CD8 + PD-1 + T cells, and CD163 + macrophages. This infiltration may be mediated by cytokines and chemokines. Collectively, these findings suggest that A3B holds potential as a novel prognostic biomarker and immunotherapeutic target for PCa.