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E-Book 3rd Congress

  • Metformin as a Potential Therapeutic Agent in Breast Cancer: Targeting miR-125a Methylation and Epigenetic Regulation
  • Fatemeh Ahmadpour1,1 Somayeh Igder2,2 Ali Reza Eftekhari Moghadam3,3 Bahman Moradipoodeh4,4 Ghorban Mohammadzadeh,5,*
    1. Nutritional Health Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran
    2. Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
    3. Department of Anatomical Science, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran
    4. Department of Laboratory Sciences, Lahijan Branch, Islamic Azad University, Lahijan, Iran
    5. Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran


  • Introduction: Breast cancer, a prevalent malignancy, has been on the rise. Molecular subtypes, including HER2-positive, pose significant challenges in treatment. Repurposing metformin as an anti-cancer agent has gained interest, particularly due to its potential impact on miRNA regulation. This study aimed to explore metformin's effects on miR-125a promoter methylation in breast cancer and its underlying mechanisms.
  • Methods: The human cell line SK-RB3, known for strong HER2 expression, was treated with varying concentrations of metformin, and cell viability was assessed using the MTT assay. Subsequent analyses explored the methylation status of the miR-125a promoter through DNA extraction and Methylation Specific PCR (MSP). Real-time PCR was employed to evaluate gene expression, and immunocytochemical staining was conducted to assess the presence of HER2 protein and Vimentin protein with Immunofluorescence test. Furthermore, in silico studies identified miR-125a-5p-regulated genes and their association with tumor pathways.
  • Results: Results indicated a dose-dependent reduction in cell viability, with IC50 values of 65 mM (48 hr) and 25 mM (72 hr). Metformin induced hypomethylation of the miR-125a promoter, resulting in a twofold increase in miR-125a expression. Additionally, it downregulated the expression of DNMT1, a DNA methyltransferase, and HER2, a key protein implicated in breast cancer. Furthermore, metformin exhibited an inhibitory effect on Vimentin, suggesting potential interference with epithelial-mesenchymal transition (EMT) processes.
  • Conclusion: This study highlights metformin's potential as an anti-cancer agent in breast cancer treatment, shedding light on its mechanisms involving miR-125a promoter methylation and its impact on key proteins like HER2 and Vimentin. Further research is warranted to fully elucidate its therapeutic benefits.
  • Keywords: Metformin, Breast Cancer, miR-125a, Methylation, HER2, DNMT1, Epigenetics