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MicroRNA-100 suppresses the migration and invasion of breast cancer cells by targeting FZD-8 and inhibiting Wnt/β-catenin signaling pathway

  • Original Article
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Tumor Biology

Abstract

Wnt/β-catenin signaling pathway plays a major role in the cancer metastasis. Several microRNAs (miRNAs) are contributed to the inhibition of breast cancer metastasis. Here, we attempted to find novel targets and mechanisms of microRNA-100 (miR-100) in regulating the migration and invasion of breast cancer cells. In this study, we found that miR-100 expression was downregulated in human breast cancer tissues and cell lines. The overexpression of miR-100 inhibited the migration and invasion of MDA-MB-231 breast cancer cells. Inversely, the downregulation of miR-100 increased the migration and invasion of MCF-7 breast cancer cells. Furthermore, FZD-8, a receptor of Wnt/β-catenin signaling pathway, was demonstrated a direct target of miR-100. The overexpression of miR-100 decreased the expression levels not only FZD-8 but also the key components of Wnt/β-catenin pathway, including β-catenin, metalloproteniase-7 (MMP-7), T-cell factor-4 (TCF-4), and lymphoid enhancing factor-1 (LEF-1), and increased the protein expression levels of GSK-3β and p-GSK-3β in MDA-MB-231 cells, and the transfection of miR-100 inhibitor in MCF-7 cells showed the opposite effects. In addition, the expression of miR-100 was negatively correlated with the FZD-8 expression in human breast cancer tissues. Overall, these findings suggest that miR-100 suppresses the migration and invasion of breast cancer cells by targeting FZD-8 and inhibiting Wnt/β-catenin signaling pathway and manipulation of miR-100 may provide a promoting therapeutic strategy for cancer breast treatment.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (Grant No. 81373427), Program for Liaoning Innovative Research Team in University, LNIRT, China (Grant No. LT2014016), the Liaoning Provincial Science and Technology Program, China (Grant No. 2013225079), Program for Liaoning Excellent Talents in University, China (Grant No. LJQ2014084), and the S&T Projects in Shenyang, China (Grant No. F14-232-6-05).

Authors’ contributions

Minjie Wei and Miao He designed the experiments. Qian Jiang, Huizhe Wu, Zhaojin Yu, Longyang Jiang, Yan Wang, and Xingyue Zong performed the experiments. Qian Jiang, Mengtao Ma, and Miao He analyzed the data. Shu Guan and Feng Jin gave technical and material support. Miao He, Qian Jiang, and Minjie Wei wrote and reviewed the manuscript.

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Authors and Affiliations

  1. Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning Province, China

    Qian Jiang, Miao He, Mengtao Ma, Huizhe Wu, Zhaojin Yu, Longyang Jiang, Yan Wang, Xingyue Zong & Minjie Wei

  2. Department of Surgical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China

    Shu Guan & Feng Jin

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  1. Qian Jiang
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  2. Miao He
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Correspondence to Minjie Wei.

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Jiang, Q., He, M., Guan, S. et al. MicroRNA-100 suppresses the migration and invasion of breast cancer cells by targeting FZD-8 and inhibiting Wnt/β-catenin signaling pathway. Tumor Biol. 37, 5001–5011 (2016). https://doi.org/10.1007/s13277-015-4342-x

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