Investigation of DNMT-mediated DNA methylation and its role in adipogenesis and breast cancer

DNA methylation, which is mediated by DNMTs, plays crucial roles in regulating gene expression and cell differentiation. In this study, we identified adipogenesis-related genes and analyzed their coexpression with DNMT isoforms in breast cancer samples from the TCGA dataset. Our findings revealed that 114 genes were coexpressed with DNMTs, among which six genes, GATA3, IRS1, LPIN1, ME3, SREBF1, and STAT1, were significantly negatively correlated with methylation and expression levels, as determined using Spearman correlation with false discovery rate correction to account for multiple testing. The differential expression patterns of these genes across breast cancer subtypes and their associations with survival outcomes were examined. Specifically, ME3 and STAT1 showed distinct associations with survival outcomes, where high ME3 expression correlated with significantly better survival rates, whereas low STAT1 expression was associated with improved prognosis. ME3 expression was significantly elevated in tumors with high adipocyte enrichment, particularly in the luminal B subtype, suggesting a subtype-specific relationship between adipogenesis and tumor behavior. Conversely, STAT1 exhibited lower expression in samples with high adipocyte counts, reinforcing its role in the tumor microenvironment. These results underscore the importance of DNMT-mediated DNA methylation in adipogenesis and breast cancer.