MicroRNA-1 down-regulates proliferation and migration of breast cancer stem cells by inhibiting the Wnt/β-catenin pathway.
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+CD24-lineage- CSCs, related to ESA+CD44-CD24+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.
Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China 150000.
Tong
T
Liu
Department of Urology, First Hospital of Jilin University, Changchun, China 130021.
Kebang
K
Hu
Department of Breast Cancer, Breast Disease and Reconstruction Center, Breast Cancer Key Lab of Dalian, the Second Hospital of Dalian Medical University, Dalian, China 114006.
Zuowei
Z
Zhao
Department of Breast Cancer, Breast Disease and Reconstruction Center, Breast Cancer Key Lab of Dalian, the Second Hospital of Dalian Medical University, Dalian, China 114006.
Guanglei
G
Chen
Department of Breast Cancer, Breast Disease and Reconstruction Center, Breast Cancer Key Lab of Dalian, the Second Hospital of Dalian Medical University, Dalian, China 114006.
Xunyan
X
Ou
Department of Breast Cancer, Breast Disease and Reconstruction Center, Breast Cancer Key Lab of Dalian, the Second Hospital of Dalian Medical University, Dalian, China 114006.
Hao
H
Zhang
Department of Breast Cancer, Breast Disease and Reconstruction Center, Breast Cancer Key Lab of Dalian, the Second Hospital of Dalian Medical University, Dalian, China 114006.
Xin
X
Zhang
Department of Breast Cancer, Breast Disease and Reconstruction Center, Breast Cancer Key Lab of Dalian, the Second Hospital of Dalian Medical University, Dalian, China 114006.
Xiaofei
X
Wei
Department of Breast Cancer, Breast Disease and Reconstruction Center, Breast Cancer Key Lab of Dalian, the Second Hospital of Dalian Medical University, Dalian, China 114006.
Dan
D
Wang
Cancer Center, the First Hospital of Jilin University, Changchun, China 130021.
Meizi
M
Cui
Department of Breast Cancer, Breast Disease and Reconstruction Center, Breast Cancer Key Lab of Dalian, the Second Hospital of Dalian Medical University, Dalian, China 114006.
Caigang
C
Liu
D000328:Adult; D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D051157:Frizzled Receptors / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D064593:Heterografts; D006801:Humans; D061986:MCF-7 Cells; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D038501:Tankyrases / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D014407:Tumor Cells, Cultured; D060449:Wnt Signaling Pathway / Q000235:genetics; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
C495270:CTNNB1 protein, human; C429034:FSD1 protein, human; C115810:FZD7 protein, human; D051157:Frizzled Receptors; D009419:Nerve Tissue Proteins; D051176:beta Catenin; C437334:TNKS2 protein, human; D038501:Tankyrases
breast cancer stem cells; miRNA profile