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bioRxiv · 10.1101/477877

miR-425 suppresses EMT and inhibits the development of TNBC (triple-negative breast cancer) by targeting TGF-β 1/SMAD 3 signaling pathway

Liu, Y.·Qiao, H.·chen, j.
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Abstract

BackgroundEMT has the crucial effect on the progression and metastasis of tumor. This work will elucidate the role of miR-425 in EMT and development of TNBC.\n\nMethodsThe differential miRNA expression among non-tumor, para-tumor (adjacent tissue of tumor) and tumor tissues was analyzed. The luciferase activities of TGF-{beta}1 3 UTR treated with miR-425 were determined. Then human breast cancer cell lines were dealt with mimics or inhibitors of miR-425, and then the cell proliferation and migration, invasion ability were assessed. The expression of TGF-{beta}1 and markers of epithelial cell and mesenchymal cell were analyzed. The influences of miR-425 on development of TNBC through inducing EMT by targeting TGF-{beta} 1 and TGF-{beta}1/SMAD3 signaling pathway in TNBC cell lines were investigated. Furthermore, Xenograft mice were used to explore the potential roles of miR-425 on EMT and development of TNBC in vivo.\n\nResultsCompared with non-tumor tissues, 9 miRNAs were upregulated and 3 miRNAs were down-regulated in tumor tissues. The relative expression of miR-425 in tumor tissues was obviously much lower than that in para-tumor and non-tumor tissues. MiR-425 suppressed TGF-{beta}1 expression, additionally inhibited expression of mesenchymal cell markers, while exerted effects on cell proliferation and migration of TNBC cell lines. Moreover, the agomir of miR-425 could protect against development process in murine TNBC xenogarft model.\n\nConclusionsOur results demonstrated that miR-425 targets to TGF-{beta}1, and was a crucial suppressor on EMT and development of TNBC through inhibiting TGF-{beta}1/SMAD3 signaling pathway. It suggested that aim at TGF-{beta}1/SMAD3 signaling pathway by enhancing relative miR-425 expression, was a feasible therapy strategy for TNBC.

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Liu, Y., Qiao, H., chen, j.. 2018-11-26. miR-425 suppresses EMT and inhibits the development of TNBC (triple-negative breast cancer) by targeting TGF-β 1/SMAD 3 signaling pathway. https://doi.org/10.1101/477877

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