DNMT1-mediated LAMA2 inhibition induces M2 macrophage polarization during prostate cancer progression.

[BACKGROUND] Prostate cancer (PCa) presents a significant risk to the health of men, and its metastatic spread greatly affects patient survival rates and quality of life. This research investigated the role of DNA methyltransferase 1 (DNMT1) in the progression of PCa.

[METHODS] By performing bioinformatics analysis and in vivo and in vitro experiments, we investigated the expression levels of DNMT1 and LAMA2 in PCa. Additionally, we evaluated how they influence the proliferation and tumor microenvironment (TME) of PCa cells.

[RESULTS] DNMT1 was upregulated in PCa, whereas LAMA2 was downregulated. DNMT1 inhibited the expression of LAMA2 by promoting methylation of the LAMA2 promoter, thereby activating the PI3K/AKT signaling pathway, promoting the proliferation of PCa cells, and inducing M2 polarization of macrophages in the TME. Furthermore, DNMT1 promoted the release of the cytokines CCL5, VEGF, MMP9, and PTX3 by PC-3 cells and affected the TME.

[CONCLUSION] This research highlights the crucial function of DNMT1 in the progression of PCa, providing new strategies for the treatment of PCa, particularly therapeutic strategies that focus on DNA methylation and tumor-associated macrophages.