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MiR-1207 overexpression promotes cancer stem cell–like traits in ovarian cancer by activating the Wnt/β-catenin signaling pathway

Wnt/β-catenin signaling pathway is strictly controlled by multiple negative regulators. However, how tumor cells override the negative regulatory effects to maintain constitutive activation of Wnt/β-catenin signaling, which is commonly observed in various cancers, remains puzzling. In current study,...

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Autores principales: Wu, Geyan, Liu, Aibin, Zhu, Jinrong, Lei, Fangyong, Wu, Shu, Zhang, Xin, Ye, Liping, Cao, Lixue, He, Shanyang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4745698/
https://www.ncbi.nlm.nih.gov/pubmed/26337084
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author Wu, Geyan
Liu, Aibin
Zhu, Jinrong
Lei, Fangyong
Wu, Shu
Zhang, Xin
Ye, Liping
Cao, Lixue
He, Shanyang
author_facet Wu, Geyan
Liu, Aibin
Zhu, Jinrong
Lei, Fangyong
Wu, Shu
Zhang, Xin
Ye, Liping
Cao, Lixue
He, Shanyang
author_sort Wu, Geyan
collection PubMed
description Wnt/β-catenin signaling pathway is strictly controlled by multiple negative regulators. However, how tumor cells override the negative regulatory effects to maintain constitutive activation of Wnt/β-catenin signaling, which is commonly observed in various cancers, remains puzzling. In current study, we reported that overexpression of miR-1207 in ovarian cancer activated Wnt/β-catenin signaling by directly targeting and suppressing secreted Frizzled-related protein 1 (SFRP1), AXIN2 and inhibitor of β-catenin and TCF-4 (ICAT), which are vital negative regulators of the Wnt/β-catenin pathway. We found that the expression of miR-1207 was ubiquitously upregulated in both ovarian cancer tissues and cells, which inversely correlated with patient overall survival. Furthermore, overexpression of miR-1207 enhanced, while silencing miR-1207 reduced, stem cell-like traits of ovarian cancer cells in vitro and in vivo, including tumor sphere formation capability and proportion of SP+ and CD133+ cells. Importantly, upregulating miR-1207 promoted, while silencing miR-1207 inhibited, the tumorigenicity of ovarian cancer cells. Hence, our results suggest that miR-1207 plays a vital role in promoting the cancer stem cell-like phenotype in ovarian cancer and might represent a potential target for anti-ovarian cancer therapy.
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spelling pubmed-47456982016-02-23 MiR-1207 overexpression promotes cancer stem cell–like traits in ovarian cancer by activating the Wnt/β-catenin signaling pathway Wu, Geyan Liu, Aibin Zhu, Jinrong Lei, Fangyong Wu, Shu Zhang, Xin Ye, Liping Cao, Lixue He, Shanyang Oncotarget Research Paper Wnt/β-catenin signaling pathway is strictly controlled by multiple negative regulators. However, how tumor cells override the negative regulatory effects to maintain constitutive activation of Wnt/β-catenin signaling, which is commonly observed in various cancers, remains puzzling. In current study, we reported that overexpression of miR-1207 in ovarian cancer activated Wnt/β-catenin signaling by directly targeting and suppressing secreted Frizzled-related protein 1 (SFRP1), AXIN2 and inhibitor of β-catenin and TCF-4 (ICAT), which are vital negative regulators of the Wnt/β-catenin pathway. We found that the expression of miR-1207 was ubiquitously upregulated in both ovarian cancer tissues and cells, which inversely correlated with patient overall survival. Furthermore, overexpression of miR-1207 enhanced, while silencing miR-1207 reduced, stem cell-like traits of ovarian cancer cells in vitro and in vivo, including tumor sphere formation capability and proportion of SP+ and CD133+ cells. Importantly, upregulating miR-1207 promoted, while silencing miR-1207 inhibited, the tumorigenicity of ovarian cancer cells. Hence, our results suggest that miR-1207 plays a vital role in promoting the cancer stem cell-like phenotype in ovarian cancer and might represent a potential target for anti-ovarian cancer therapy. Impact Journals LLC 2015-08-17 /pmc/articles/PMC4745698/ /pubmed/26337084 Text en Copyright: © 2015 Wu 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
Wu, Geyan
Liu, Aibin
Zhu, Jinrong
Lei, Fangyong
Wu, Shu
Zhang, Xin
Ye, Liping
Cao, Lixue
He, Shanyang
MiR-1207 overexpression promotes cancer stem cell–like traits in ovarian cancer by activating the Wnt/β-catenin signaling pathway
title MiR-1207 overexpression promotes cancer stem cell–like traits in ovarian cancer by activating the Wnt/β-catenin signaling pathway
title_full MiR-1207 overexpression promotes cancer stem cell–like traits in ovarian cancer by activating the Wnt/β-catenin signaling pathway
title_fullStr MiR-1207 overexpression promotes cancer stem cell–like traits in ovarian cancer by activating the Wnt/β-catenin signaling pathway
title_full_unstemmed MiR-1207 overexpression promotes cancer stem cell–like traits in ovarian cancer by activating the Wnt/β-catenin signaling pathway
title_short MiR-1207 overexpression promotes cancer stem cell–like traits in ovarian cancer by activating the Wnt/β-catenin signaling pathway
title_sort mir-1207 overexpression promotes cancer stem cell–like traits in ovarian cancer by activating the wnt/β-catenin signaling pathway
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4745698/
https://www.ncbi.nlm.nih.gov/pubmed/26337084
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