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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 b...

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Autores principales: Liu, Tong, Hu, Kebang, Zhao, Zuowei, Chen, Guanglei, Ou, Xunyan, Zhang, Hao, Zhang, Xin, Wei, Xiaofei, Wang, Dan, Cui, Meizi, Liu, Caigang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747178/
https://www.ncbi.nlm.nih.gov/pubmed/26497855
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author Liu, Tong
Hu, Kebang
Zhao, Zuowei
Chen, Guanglei
Ou, Xunyan
Zhang, Hao
Zhang, Xin
Wei, Xiaofei
Wang, Dan
Cui, Meizi
Liu, Caigang
author_facet Liu, Tong
Hu, Kebang
Zhao, Zuowei
Chen, Guanglei
Ou, Xunyan
Zhang, Hao
Zhang, Xin
Wei, Xiaofei
Wang, Dan
Cui, Meizi
Liu, Caigang
author_sort Liu, Tong
collection PubMed
description 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.
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spelling pubmed-47471782016-03-25 MicroRNA-1 down-regulates proliferation and migration of breast cancer stem cells by inhibiting the Wnt/β-catenin pathway Liu, Tong Hu, Kebang Zhao, Zuowei Chen, Guanglei Ou, Xunyan Zhang, Hao Zhang, Xin Wei, Xiaofei Wang, Dan Cui, Meizi Liu, Caigang Oncotarget Research Paper 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. Impact Journals LLC 2015-10-19 /pmc/articles/PMC4747178/ /pubmed/26497855 Text en Copyright: © 2015 Liu et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Liu, Tong
Hu, Kebang
Zhao, Zuowei
Chen, Guanglei
Ou, Xunyan
Zhang, Hao
Zhang, Xin
Wei, Xiaofei
Wang, Dan
Cui, Meizi
Liu, Caigang
MicroRNA-1 down-regulates proliferation and migration of breast cancer stem cells by inhibiting the Wnt/β-catenin pathway
title MicroRNA-1 down-regulates proliferation and migration of breast cancer stem cells by inhibiting the Wnt/β-catenin pathway
title_full MicroRNA-1 down-regulates proliferation and migration of breast cancer stem cells by inhibiting the Wnt/β-catenin pathway
title_fullStr MicroRNA-1 down-regulates proliferation and migration of breast cancer stem cells by inhibiting the Wnt/β-catenin pathway
title_full_unstemmed MicroRNA-1 down-regulates proliferation and migration of breast cancer stem cells by inhibiting the Wnt/β-catenin pathway
title_short MicroRNA-1 down-regulates proliferation and migration of breast cancer stem cells by inhibiting the Wnt/β-catenin pathway
title_sort microrna-1 down-regulates proliferation and migration of breast cancer stem cells by inhibiting the wnt/β-catenin pathway
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747178/
https://www.ncbi.nlm.nih.gov/pubmed/26497855
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