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

// Feng Liu 1 , Yang Liu 1 , Jingling Shen 2 , Guoqiang Zhang 1 , Jiguang Han 1 1 Department of Breast Surgery, Cancer Hospital of Harbin Medical University, Harbin 150081, China 2 Department 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.