MicroRNA-224 inhibits proliferation and migration of breast cancer cells by down-regulating Fizzled 5 expression.
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 fizzled 5-regulated luciferase activity in 293T cells, fizzled 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.
Department of Breast Surgery, Cancer Hospital of Harbin Medical University, Harbin 150081, China.
Feng
F
Liu
Department of Breast Surgery, Cancer Hospital of Harbin Medical University, Harbin 150081, China.
Yang
Y
Liu
Department of Histology and Embryology, Harbin Medical University, Harbin 150081, China.
Jingling
J
Shen
Department of Breast Surgery, Cancer Hospital of Harbin Medical University, Harbin 150081, China.
Guoqiang
G
Zhang
Department of Breast Surgery, Cancer Hospital of Harbin Medical University, Harbin 150081, China.
Jiguang
J
Han
D000328:Adult; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D051927:CD24 Antigen / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D051157:Frizzled Receptors / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000473:pathology; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
D051927:CD24 Antigen; C497889:CD24 protein, human; C497483:CD44 protein, human; C495270:CTNNB1 protein, human; C498589:FZD5 protein, human; D051157:Frizzled Receptors; D018960:Hyaluronan Receptors; C546140:MIRN224 microRNA, human; D035683:MicroRNAs; D051176:beta Catenin
MiR-224; Wnt/β-catenin signaling; breast cancer cells; migration; proliferation