metformin as a potential therapeutic agent in breast cancer: targeting mir-125a methylation and epigenetic regulation

Breast cancer, characterized by genetic diversity and molecular subtypes, presents significant treatment challenges, especially in human epidermal growth factor receptor type 2 (her2)-positive cases, which are associated with poor prognosis. metformin, widely known for its antidiabetic effects, has emerged as a promising candidate for cancer therapy. this study investigates the effect of metformin on mir-125a promoter methylation and its subsequent impact on the her2 signaling pathway in her2-positive breast cancer cells (sk-br3). sk-br3 cells were cultured and treated with various concentrations of metformin to assess its effects on cell viability, dna methylation, her2, and dna methyltransferase 1 (dnmt1) expression. molecular analyses focus on the mir-125a signaling pathway modulation, dna methylation, mrna expression of dnmt1, and protein level of her2. research showed a dose-dependent reduction in cell viability, with ic50 values from 65 mm at 48 hours to 35 mm at 72 hours. metformin treatment led to demethylation of the mir-125a promoter, which increased mir-125a expression and subsequently reduced her2 levels. this suggests that metformin exerts its anticancer effects partly by regulation of the mir-125a-her2 axis. additionally, metformin inhibited vimentin expression, indicating its potential to interfere with epithelial-mesenchymal transition (emt) processes. metformin may serve as a targeted therapeutic agent in her2-positive breast cancer by modulating the mir-125a-her2 axis and influencing on the epigenetic and emt regulation. further research is warranted to elucidate the therapeutic potential of metformin through these mechanisms.