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Tumour Biol. 2016 Apr;37(4):5001-11. doi: 10.1007/s13277-015-4342-x. Epub 2015 Nov 4.

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

Author information

1
Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning Province, People's Republic of China.
2
Department of Surgical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.
3
Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning Province, People's Republic of China. weiminjiecmu@163.com.

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.

KEYWORDS:

Breast cancer; FZD-8; Invasion; MiR-100; Migration; Wnt/β-catenin signaling pathway

PMID:
26537584
DOI:
10.1007/s13277-015-4342-x
[Indexed for MEDLINE]

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