The anticancer activity of metformin through microRNAs modulation

Metformin is considered one of the common anti-hyperglycemic and cost-benefit drugs to treat patients with type II diabetes and polycystic ovary syndrome in women. Metformin has important role by enhancing glucose uptake into the skeletal muscle and inhibiting hepatic gluconeogenesis and cellular energy homeostasis. The availability of glucose for glycolytic ATP generation, lipid and cholesterol synthesis plays a pivotal role in cancer development and progression. Metformin impacts on cell proliferation through the modulation of microRNAs deregulation and their mRNA targets in both cancer and diabetic cell systems and low expression of DICER is correlated with cancer development. The current state and application of metformin in clinical practice including:a) The increase of insulin- like growth factor binding protein 1 (IGFBP1), to limit the binding between IGF1 and their receptors and consequently the production of androgen. b) Inhibition of IGF1R sensitized and circulating growth factors to the cytotoxic effects of chemotherapy treatment. c) Inhibiting the tumor necrosis factor alpha (TNFα) production in human lymphocytes. d) Modulation the activity of checkpoints, which results in an increased sensitivity of cancer cells against DNA damage and inhibited the growth of carcinoma by inducing G1 cell cycle arrest. e) Modulation of insulin signalling and lipid homeostasis by mir-33b and cholesterol homeostasis by mir-33b regulation. f) Up-regulation of miR-26a, miR-192 and let-7c to inhibit cell proliferation, invasion, migration and increased cell apoptosis. g) Down-regulation of miR-222 to inhibit cell growth and cell cycle progression via direct of p27, p57 and PTEN. h) Modulation of miR-140, miR-222, miR-142 and miR-192 in plasma samples collected from type 2diabetes.Therefore, metformin can perform anti anticancer effects and reprogram cancer metabolism through miRNA modulation and expression of DICER.

کلیدواژه ها:

Metformin ، anticancer ، microRNAs