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A robust screening method for dietary agents that activate tumour-suppressor microRNAs

Certain dietary agents, such as natural products, have been reported to show anti-cancer effects. However, the underlying mechanisms of these substances in human cancer remain unclear. We recently found that resveratrol exerts an anti-cancer effect by upregulating tumour-suppressor microRNAs (miRNAs...

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Autores principales: Hagiwara, Keitaro, Gailhouste, Luc, Yasukawa, Ken, Kosaka, Nobuyoshi, Ochiya, Takahiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4589759/
https://www.ncbi.nlm.nih.gov/pubmed/26423775
http://dx.doi.org/10.1038/srep14697
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author Hagiwara, Keitaro
Gailhouste, Luc
Yasukawa, Ken
Kosaka, Nobuyoshi
Ochiya, Takahiro
author_facet Hagiwara, Keitaro
Gailhouste, Luc
Yasukawa, Ken
Kosaka, Nobuyoshi
Ochiya, Takahiro
author_sort Hagiwara, Keitaro
collection PubMed
description Certain dietary agents, such as natural products, have been reported to show anti-cancer effects. However, the underlying mechanisms of these substances in human cancer remain unclear. We recently found that resveratrol exerts an anti-cancer effect by upregulating tumour-suppressor microRNAs (miRNAs). In the current study, we aimed to identify new dietary products that have the ability to activate tumour-suppressor miRNAs and that therefore may serve as novel tools for the prevention and treatment of human cancers. We describe the generation and use of an original screening system based on a luciferase-based reporter vector for monitoring miR-200c tumour-suppressor activity. By screening a library containing 139 natural substances, three natural compounds — enoxolone, magnolol and palmatine chloride — were identified as being capable of inducing miR-200c expression in breast cancer cells at 10 μM. Moreover, these molecules suppressed the invasiveness of breast cancer cells in vitro. Next, we identified a molecular pathway by which the increased expression of miR-200c induced by natural substances led to ZEB1 inhibition and E-cadherin induction. These results indicate that our method is a valuable tool for a fast identification of natural molecules that exhibit tumour-suppressor activity in human cancer through miRNA activation.
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spelling pubmed-45897592015-10-13 A robust screening method for dietary agents that activate tumour-suppressor microRNAs Hagiwara, Keitaro Gailhouste, Luc Yasukawa, Ken Kosaka, Nobuyoshi Ochiya, Takahiro Sci Rep Article Certain dietary agents, such as natural products, have been reported to show anti-cancer effects. However, the underlying mechanisms of these substances in human cancer remain unclear. We recently found that resveratrol exerts an anti-cancer effect by upregulating tumour-suppressor microRNAs (miRNAs). In the current study, we aimed to identify new dietary products that have the ability to activate tumour-suppressor miRNAs and that therefore may serve as novel tools for the prevention and treatment of human cancers. We describe the generation and use of an original screening system based on a luciferase-based reporter vector for monitoring miR-200c tumour-suppressor activity. By screening a library containing 139 natural substances, three natural compounds — enoxolone, magnolol and palmatine chloride — were identified as being capable of inducing miR-200c expression in breast cancer cells at 10 μM. Moreover, these molecules suppressed the invasiveness of breast cancer cells in vitro. Next, we identified a molecular pathway by which the increased expression of miR-200c induced by natural substances led to ZEB1 inhibition and E-cadherin induction. These results indicate that our method is a valuable tool for a fast identification of natural molecules that exhibit tumour-suppressor activity in human cancer through miRNA activation. Nature Publishing Group 2015-10-01 /pmc/articles/PMC4589759/ /pubmed/26423775 http://dx.doi.org/10.1038/srep14697 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Hagiwara, Keitaro
Gailhouste, Luc
Yasukawa, Ken
Kosaka, Nobuyoshi
Ochiya, Takahiro
A robust screening method for dietary agents that activate tumour-suppressor microRNAs
title A robust screening method for dietary agents that activate tumour-suppressor microRNAs
title_full A robust screening method for dietary agents that activate tumour-suppressor microRNAs
title_fullStr A robust screening method for dietary agents that activate tumour-suppressor microRNAs
title_full_unstemmed A robust screening method for dietary agents that activate tumour-suppressor microRNAs
title_short A robust screening method for dietary agents that activate tumour-suppressor microRNAs
title_sort robust screening method for dietary agents that activate tumour-suppressor micrornas
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4589759/
https://www.ncbi.nlm.nih.gov/pubmed/26423775
http://dx.doi.org/10.1038/srep14697
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