MiR-92b inhibited cells EMT by targeting Gabra3 and predicted prognosis of triple negative breast cancer patients

Y.-Y. Li, X.-H. Zheng, A.-P. Deng, Y. Wang, J. Liu, Q. Zhou, G.-Y. Cheng, Q. Jiang

Department of Pharmacy, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. yuls34@163.com

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• Oncology

OBJECTIVE: Triple negative breast cancer (TNBC) is a subtype of breast cancer without the three markers, which has a poor prognosis than other types. Recently, studies have identified that microRNA-92b (miR-92b) acted as potential oncogene in tumor progression, however, the biological roles of miR-92b in TNBC remain unknown. The purpose of this study was to investigate the functions of miR-92b and verify its effect on the regulation of Gabra3 in TNBC.

MATERIALS AND METHODS: Dual-Luciferase reporter assay was recruited to confirm whether miR-92b directly binds to the 3′-untranslated region (3′-UTR) of Gabra3 mRNA in TNBC. Transwell assay was employed to analyze the capacities of migration and invasion. Western blot was applied to evaluate the expression of the special proteins that including Gabra3, epithelial-mesenchymal transition (EMT) markers and GAPDH.

RESULTS: We demonstrated that miR-92b was remarkably low expressed in TNBC tissues and cell lines, and particularly in inhibiting the migration, invasion and EMT of TNBC cells. On the contrary, Gabra3 was significantly overexpressed in TNBC tissues and cell lines in comparison with the corresponding paracancerous tissues and the normal breast epithelial cell line. The expression of miR-92b had a negative correlation with the expression of Gabra3 in TNBC tissues. Downregulation of Gabra3 could inhibit the migration, invasion and EMT of TNBC cells. MiR-92b mediated the expression of Gabra3 through directly binding to the 3′-UTR of Gabra3 mRNA. In addition, low expression of miR-92b or overexpression of Gabra3 predicted poor prognosis of TNBC patients.

CONCLUSIONS: MiR-92b inhibited the migration and invasion-mediated EMT through directly targeting the 3′-UTR of Gabra3 mRNA in triple negative breast cancer. The newly identified miR-92b/Gabra3 axis may make it to be a new target for clinical diagnosis and treatment of TNBC

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