MiR-566 protects the malignant progression of breast cancer by negatively regulating WNT6

M.-C. Zhao, M.-M. Zhang, T. Li, Z.-H. Tao, Y.-Q. Du, L.-P. Wang, J. Zhang, B.-Y. Wang, X.-C. Hu

Department of Medical Oncology, Fudan University Shanghai Cancer Center, Fudan University School of Medicine, Shanghai, China. huxichun2017@163.com

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• Oncology

OBJECTIVE: To elucidate the relationship between microRNA-566 (miR-566) and prognosis in breast cancer (BC) and to clarify the influences of miR-566 and WNT6 in its locus region on BC progression.

PATIENTS AND METHODS: MiR-566 and WNT6 levels in 44 pairs of BC samples were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The influences of miR-566 on clinical features and prognosis in BC patients were analyzed. According to the differential expressions of miR-566 in the tested BC cell lines, MDA-MB-231 and MCF-7 cells were selected for generating miR-566 knockdown and overexpression models, respectively. Cell counting kit-8 (CCK-8), 5-Ethynyl-2’-deoxyuridine (EdU) and transwell assays were conducted to explore the role of miR-566 in BC cell functions. Besides, the regulatory interaction between miR-566 and its downstream gene WNT6 was assessed by performing Dual-Luciferase reporter assay. Finally, the co-regulation of miR-566 and WNT6 in BC cell functions was examined.

RESULTS: MiR-566 was downregulated in BC tissues. BC patients with a low expression level of miR-566 were prone to suffering a large tumor size, advanced tumor grade, high incidence of lymphatic metastasis and poor prognosis. Overexpression of miR-566 weakened proliferative and migratory abilities in MCF-7 cells, whereas knockdown of miR-566 produced the opposite results in MDA-MB-231 cells. WNT6 was the target gene binding to miR-566, and they displayed a negative expression correlation in BC tissues. Regulatory effects of miR-566 on BC progression could be reversed by WNT6.

CONCLUSIONS: MiR-566 is closely related to tumor size, tumor grade, lymphatic metastasis and prognosis in BC. It protects the malignant progression of BC by negatively regulating WNT6.

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