repression of tgf-β signaling in breast cancer cells by mir-302/367 cluster

Objective: epigenetic alterations of the malignantly transformed cells have increasingly been regarded as an important event in the carcinogenic development. induction of some mirnas such as mir-302/367 cluster has been shown to induce reprogramming of breast cancer cells and exert a tumor suppressive role by induction of mesenchymal to epithelial transition, apoptosis and a lower proliferation rate. here, we aimed to investigate the impact of mir-302/367 overexpression on transforming growth factor-beta (tgf-β) signaling and how this may contribute to tumor suppressive effects of mir-302/367 cluster. materials and methods: in this experimental study, mda-mb-231 and sk-br-3 breast cancer cells were cultured and transfected with mir-302/367 expressing lentivector. the impact of mir-302/367 overexpression on several mediators of tgf-β signaling and cell cycle was assessed by quantitative real-time polymerase chain reaction (qpcr) and flow cytometry. results: ectopic expression of mir-302/367 cluster downregulated expression of some downstream elements of tgf-β pathway in mda-mb-231 and sk-br-3 breast cancer cell lines. overexpression of mir-302/367 cluster inhibited proliferation of the breast cancer cells by suppressing the s-phase of cell cycle which was in accordance with inhibition of tgf-β pathway. conclusion: tgf-β signaling is one of the key pathways in tumor progression and a general suppression of tgf-β mediators by the pleiotropically acting mir-302/367 cluster may be one of the important reasons for its anti-tumor effects in breast cancer cells.