Repression of TGFβ Signaling in Breast Cancer Cells by miR302/367 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 miR302/367 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 miR302/367 overexpression on transforming growth factorbeta (TGFβ) signaling and how this may contribute to tumor suppressive effects of miR302/367 cluster. Materials and Methods In this experimental study, MDAMB231 and SKBR3 breast cancer cells were cultured and transfected with miR302/367 expressing lentivector. The impact of miR302/367 overexpression on several mediators of TGFβ signaling and cell cycle was assessed by quantitative realtime polymerase chain reaction (qPCR) and flow cytometry. Results Ectopic expression of miR302/367 cluster downregulated expression of some downstream elements of TGFβ pathway in MDAMB231 and SKBR3 breast cancer cell lines. Overexpression of miR302/367 cluster inhibited proliferation of the breast cancer cells by suppressing the Sphase of cell cycle which was in accordance with inhibition of TGFβ pathway. ConclusionTGFβ signaling is one of the key pathways in tumor progression and a general suppression of TGFβ mediators by the pleiotropically acting miR302/367 cluster may be one of the important reasons for its antitumor effects in breast cancer cells.