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

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-?) 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-? 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-? 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-? pathway. Conclusion:TGF-? signaling is one of the key pathways in tumor progression and a general suppression of TGF-? 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.

SUBMITTER: Ahmadalizadeh Khanehsar M 

PROVIDER: S-EPMC6722449 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature