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

Ahmadalizadeh Khanehsar, Mona; Hoseinbeyki, Moslem; Fakhr Taha, Masoumeh; Javeri, Arash

doi:10.22074/cellj.2020.6193

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

Document Type : Original Article

Authors

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 Az

² Department of Stem Cells and Regenerative Medicine, Institute for Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran

10.22074/cellj.2020.6193

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.

Keywords