Oncotarget

Research Papers:

MicroRNA-224 inhibits proliferation and migration of breast cancer cells by down-regulating Frizzled 5 expression

Feng Liu, Yang Liu, Jingling Shen, Guoqiang Zhang _ and Jiguang Han

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Oncotarget. 2016; 7:49130-49142. https://doi.org/10.18632/oncotarget.9734

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Abstract

Feng Liu1, Yang Liu1, Jingling Shen2, Guoqiang Zhang1, Jiguang Han1

1Department of Breast Surgery, Cancer Hospital of Harbin Medical University, Harbin 150081, China

2Department of Histology and Embryology, Harbin Medical University, Harbin 150081, China

Correspondence to:

Guoqiang Zhang, email: guoqiangzhangh@163.com

Keywords: MiR-224, Wnt/β-catenin signaling, proliferation, migration, breast cancer cells

Received: November 14, 2015     Accepted: April 25, 2016     Published: May 31, 2016

ABSTRACT

The Wnt/β-catenin signaling is crucial for the proliferation and migration of breast cancer cells. However, the expression of microRNA-224 (miR-224) in the different types of breast cancers and its role in the Wnt/β-catenin signaling and the proliferation and migration of breast cancer cells are poorly understood. In this study, the levels of miR-224 in different types of breast cancer tissues and cell lines were examined by quantitative RT-PCR and the potential targets of miR-224 in the Wnt/β-catenin signaling were investigated. The effects of altered miR-224 expression on the frequency of CD44+CD24 cancer stem-like cells (CSC), proliferation and migration of MCF-7 and MDA-MB-231 cells were examined by flow cytometry, MTT and transwell migration. We found that the levels of miR-224 expression in different types of breast cancer tissues and cell lines were associated inversely with aggressiveness of breast cancers. Enhanced miR-224 expression significantly reduced the Frizzled 5-regulated luciferase activity in 293T cells, Frizzled 5 expression in MCF-7 and MDA-MB-231 cells, the β-dependent luciferase activity in MCF-7 cells, and the nuclear translocation of β-catenin in MDA-MB-231 cells. miR-224 inhibition significantly increased the percentages of CSC in MCF-7 cells and enhanced proliferation and migration of MCF-7 cells. Enhanced miR-224 expression inhibited proliferation and migration of MDA-MB-231 cells, and the growth of implanted breast cancers in vivo. Induction of Frizzled 5 over-expression mitigated the miR-224-mediated inhibition of breast cancer cell proliferation. Collectively, these data indicated that miR-224 down-regulated the Wnt/β-catenin signaling possibly by binding to Frizzled 5 and inhibited proliferation and migration of breast cancer cells.


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