MicroRNA-296 functions as a tumor suppressor in breast cancer by targeting FGFR1 and regulating the Wnt/β-catenin signaling pathway

W.-M. Sun, W. Tao, J.-C. Li, D.-M. Zhu, Y. Miao

Department of General Surgery Breast Ward, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China. miaoyejz@126.com

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• Oncology

OBJECTIVE: Breast cancer (BC) is a common malignancy all over the world. However, the detailed mechanism underlying BC progression remains incompletely understood. MicroRNAs (miRNAs) have been observed to play crucial roles in tumorigenesis. The present study aimed to determine the expression and function of miR-296 in BC.

PATIENTS AND METHODS: MiR-296 expressions in BC tissue samples and cell lines were examined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). After that, we performed functional assays, including MTT (3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assays and transwell assays, to show the functions of miR-296 in BC cell proliferation, invasion and migration. Immunological histological chemistry (IHC) assays were carried out to detect the expression levels of fibroblast growth factor receptor 1 (FGFR1) in BC tissue samples. Western blot was used to explore potential mechanisms of miR-296 in regulating BC progression. A Luciferase reporter assay was carried out to confirm the target gene of miR-296.

RESULTS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) results demonstrated a significant decrease of miR-296 expressions in BC when compared to the corresponding normal controls. In addition, the decreased miR-296 was correlated with the malignant phenotypes and poorer prognosis of BC patients. The functional assays indicated that miR-296 restoration could repress the proliferation, invasion and migration abilities of BC cells. Moreover, the results of the current study revealed that miR-296 exerted the repressive functions in BC cells via regulating FGFR1, the Wnt/β-catenin signaling pathway and EMT. Additionally, miR-296 up-regulation could inhibit in vivo BC cell growth.

CONCLUSIONS: All these findings indicated that miR-296 exerted anti-BC functions, providing novel therapeutic strategies in BC treatment.

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