Repression of TGF-β Signaling in Breast Cancer Cells by miR-302/367 Cluster


Mona Ahmadalizadeh Khanehsar, M.Sc, 1,2Moslem Hoseinbeyki, M.Sc, 1Masoumeh Fakhr Taha, Ph.D, 1Arash Javeri, M.D., Ph.D., 1,*
Department of Stem Cells and Regenerative Medicine, Institute for Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran
Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran
Department of Stem Cells and Regenerative Medicine, Institute for Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran
Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran
*Corresponding Address: P.O. Box: 14965-161 Department of Stem Cells and Regenerative Medicine Institute for Medical Biotechnology National Institute of Genetic Engineering and Biotechnology (NIGEB) Pajoohesh Blvd. Tehran Iran Email:arashj@nigeb.ac.ir
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Ahmadalizadeh Khanehsar Mona, Hoseinbeyki Moslem, Fakhr Taha Masoumeh, Javeri Arash. Repression of TGF-β Signaling in Breast Cancer Cells by miR-302/367 Cluster. Cell J. 2020; 21(4): 444-450.

Abstract

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.