Oncotarget

Research Papers:

MicroRNA-1 down-regulates proliferation and migration of breast cancer stem cells by inhibiting the Wnt/β-catenin pathway

Tong Liu, Kebang Hu, Zuowei Zhao, Guanglei Chen, Xunyan Ou, Hao Zhang, Xin Zhang, Xiaofei Wei, Dan Wang, Meizi Cui _ and Caigang Liu

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Oncotarget. 2015; 6:41638-41649. https://doi.org/10.18632/oncotarget.5873

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Abstract

Tong Liu1, Kebang Hu2, Zuowei Zhao3, Guanglei Chen3, Xunyan Ou3, Hao Zhang3, Xin Zhang3, Xiaofei Wei3, Dan Wang3, Meizi Cui4, Caigang Liu3

1Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China 150000

2Department of Urology, First Hospital of Jilin University, Changchun, China 130021

3Department of Breast Cancer, Breast Disease and Reconstruction Center, Breast Cancer Key Lab of Dalian, the Second Hospital of Dalian Medical University, Dalian, China 114006

4Cancer Center, the First Hospital of Jilin University, Changchun, China 130021

Correspondence to:

Caigang Liu, e-mail: [email protected]

Meizi Cui, e-mail: [email protected]

Keywords: breast cancer stem cells, miRNA profile

Received: May 25, 2015     Accepted: October 09, 2015     Published: October 19, 2015

ABSTRACT

We investigated the miRNA profiles of breast cancer stem cells (CSCs) and non-CSC tumor cells by miRNA microarray and determined the effect of altered miR-1 expression on proliferation and migration of breast CSCs. The potential targets of miR-1 in the Wnt/β-catenin signaling were characterized by bioinformatics analysis and luciferase assay. We found that 14 miRNAs were up-regulated and 13 were down-regulated in the ESA+CD44+CD24lineage CSCs, related to ESA+CD44CD24+lineage non-CSC tumor cells. The miR-1 expression was associated inversely with aggressiveness of breast cancers. Furthermore, enhanced miR-1 expression decreased the percentages of SKBR3/CSCs and miR-1 inhibition increased the percentages of MCF-7/CSCs. Enhanced miR-1 expression significantly reduced the Frizzled 7 and Tankyrase-2 (TNKS2)-regulated luciferase activity in 293T cells and decreased Frizzled 7, TNKS2, c-Myc, octamer-binding transcription factor 4 (Oct4) and Nanog expression and the ratios of nuclear to cytoplasmic β-catenin as well as β-catenin-dependent luciferase activity in breast CSCs in vitro. miR-1 inhibited proliferation, migration and wound healing of breast CSCs in vitro. Enhanced miR-1 expression inhibited the growth of implanted MCF-7/CSCs while miR-1 inhibition promoted the growth of implanted MCF-7/CSCs in vivo. Our data indicate that miR-1 down-regulates breast CSC stemness, proliferation and migration by targeting the Frizzled 7 and TNKS2 to inhibit the Wnt/β-catenin signaling.


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