Effect of miR-34a on resistance to sunitinib in breast cancer by regulating the Wnt/β-catenin signaling pathway

L.-G. Gong, J.-C. Shi, J. Shang, J.-G. Hao, X. Du

Department of Breast Surgery, Yantaishan Hospital, Yantai, China. dxsj22@126.com

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• Oncology

OBJECTIVE: The aim of this study was to investigate the influence of micro ribonucleic acid (miR)-34a on resistance to sunitinib in breast cancer, and to explore its possible underlying mechanism.

MATERIALS AND METHODS: Breast cancer MCF-7 cells were transfected with miR-34a inhibitor or mimics to downregulate or upregulate the expression of miR-34a. Then, the transfected cells were treated with sunitinib. Next, transwell assay was applied to detect the changes in cell invasion ability. Cell viability was measured via cell counting kit-8 (CCK8) assay. Dual-Luciferase reporter gene assay was employed to determine the interaction between miR-34a and the Wnt/β-catenin signaling pathway. The immunoblotting assay was used to measure the expression changes of proteins in the pathway.

RESULTS: The overexpression of miR-34a significantly reduced the invasive ability of MCF-7 cells after treatment with sunitinib. After miR-34a expression was downregulated, the sensitivity of MCF-7 cells to sunitinib was significantly lowered. MiR-34a interacted with the 3’-untranslated region (3’-UTR) on Wnt1. Meanwhile, the overexpression of miR-34a remarkably downregulated the messenger RNA (mRNA) and the protein levels of Wnt1, whereas upregulated the expressions of Wnt1 and β-catenin.

CONCLUSIONS: MiR-34a affects the sensitivity to sunitinib in breast cancer by regulating the Wnt/β-catenin signaling pathway.

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