MiR-425 suppresses EMT and the development of TNBC (triple-negative breast cancer) by targeting the TGF-β 1/SMAD 3 signaling pathway. Issue 1 (21st December 2018)

• Record Type: Journal Article
• Authors: Liu, Yingping; Chen, Jinglong
• Is Part Of: RSC advances. Volume 9:Issue 1(2019)
• Page Start: 151
• Page End: 165
• Publication Date: 2018-12-21
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c8ra08872a
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : EMT has a crucial effect on the progression and metastasis of tumors. Abstract : Background : EMT has a crucial effect on the progression and metastasis of tumors. This work will elucidate the role of miR-425 in EMT and the development of TNBC. Methods : The differential miRNA expression among non-tumor, para-tumor (adjacent tissue of tumor) and tumor tissues was analyzed. The luciferase activities of TGF-β1 3′UTR treated with miR-425 were determined. Then human breast cancer cell lines were treated with mimics or inhibitors of miR-425, and then the cell proliferation and migration, and invasion ability were assessed. The expression of TGF-β1 and markers of epithelial cells and mesenchymal cells were analyzed. The influences of miR-425 on the development of TNBC through inducing EMT by targeting the TGF-β1/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 the development of TNBC in vivo . Results : Compared 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-β1 expression, and further inhibited expression of mesenchymal cell markers, while it exerted effects on cell proliferation and migration of TNBC cell lines. Moreover, the agomir of miR-425 could protect against the development process in a murine TNBC xenograft model. Conclusions : Our results demonstrated that miR-425 targets TGF-β1, and was a crucial suppressor on EMT and the development of TNBC through inhibiting the TGF-β1/SMAD3 signaling pathway. This suggests that aiming at the TGF-β1/SMAD3 signaling pathway by enhancing relative miR-425 expression, is a feasible therapy strategy for TNBC.