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Targeting Notch signalling by the conserved miR-8/200 microRNA family in development and cancer cells
Notch signalling is crucial for the correct development and growth of numerous organs and tissues, and when subverted it can cause cancer. Loss of miR-8/200 microRNAs (miRNAs) is commonly observed in advanced tumours and correlates with their invasion and acquisition of stem-like properties. Here, w...
Autores principales: | , , |
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3041954/ https://www.ncbi.nlm.nih.gov/pubmed/21224847 http://dx.doi.org/10.1038/emboj.2010.358 |
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author | Vallejo, Diana M Caparros, Esther Dominguez, Maria |
author_facet | Vallejo, Diana M Caparros, Esther Dominguez, Maria |
author_sort | Vallejo, Diana M |
collection | PubMed |
description | Notch signalling is crucial for the correct development and growth of numerous organs and tissues, and when subverted it can cause cancer. Loss of miR-8/200 microRNAs (miRNAs) is commonly observed in advanced tumours and correlates with their invasion and acquisition of stem-like properties. Here, we show that this miRNA family controls Notch signalling activation in Drosophila and human cells. In an overexpression screen, we identified the Drosophila miR-8 as a potent inhibitor of Notch-induced overgrowth and tumour metastasis. Gain and loss of mir-8 provoked developmental defects reminiscent of impaired Notch signalling and we demonstrated that miR-8 directly inhibits Notch ligand Serrate. Likewise, miR-200c and miR-141 directly inhibited JAGGED1, impeding proliferation of human metastatic prostate cancer cells. It has been suggested that JAGGED1 may also be important for metastases. Although in metastatic cancer cells, JAGGED1 modestly regulated ZEB1, the miR-200c's target in invasion, studies in Drosophila revealed that only concurrent overexpression of Notch and Zfh1/ZEB1 induced tumour metastases. Together, these data define a new way to attenuate or boost Notch signalling that may have clinical interest. |
format | Text |
id | pubmed-3041954 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-30419542011-03-15 Targeting Notch signalling by the conserved miR-8/200 microRNA family in development and cancer cells Vallejo, Diana M Caparros, Esther Dominguez, Maria EMBO J Article Notch signalling is crucial for the correct development and growth of numerous organs and tissues, and when subverted it can cause cancer. Loss of miR-8/200 microRNAs (miRNAs) is commonly observed in advanced tumours and correlates with their invasion and acquisition of stem-like properties. Here, we show that this miRNA family controls Notch signalling activation in Drosophila and human cells. In an overexpression screen, we identified the Drosophila miR-8 as a potent inhibitor of Notch-induced overgrowth and tumour metastasis. Gain and loss of mir-8 provoked developmental defects reminiscent of impaired Notch signalling and we demonstrated that miR-8 directly inhibits Notch ligand Serrate. Likewise, miR-200c and miR-141 directly inhibited JAGGED1, impeding proliferation of human metastatic prostate cancer cells. It has been suggested that JAGGED1 may also be important for metastases. Although in metastatic cancer cells, JAGGED1 modestly regulated ZEB1, the miR-200c's target in invasion, studies in Drosophila revealed that only concurrent overexpression of Notch and Zfh1/ZEB1 induced tumour metastases. Together, these data define a new way to attenuate or boost Notch signalling that may have clinical interest. Nature Publishing Group 2011-02-16 2011-01-11 /pmc/articles/PMC3041954/ /pubmed/21224847 http://dx.doi.org/10.1038/emboj.2010.358 Text en Copyright © 2011, European Molecular Biology Organization http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Noncommercial Share Alike 3.0 Unported License, which allows readers to alter, transform, or build upon the article and then distribute the resulting work under the same or similar license to this one. The work must be attributed back to the original author and commercial use is not permitted without specific permission. |
spellingShingle | Article Vallejo, Diana M Caparros, Esther Dominguez, Maria Targeting Notch signalling by the conserved miR-8/200 microRNA family in development and cancer cells |
title | Targeting Notch signalling by the conserved miR-8/200 microRNA family in development and cancer cells |
title_full | Targeting Notch signalling by the conserved miR-8/200 microRNA family in development and cancer cells |
title_fullStr | Targeting Notch signalling by the conserved miR-8/200 microRNA family in development and cancer cells |
title_full_unstemmed | Targeting Notch signalling by the conserved miR-8/200 microRNA family in development and cancer cells |
title_short | Targeting Notch signalling by the conserved miR-8/200 microRNA family in development and cancer cells |
title_sort | targeting notch signalling by the conserved mir-8/200 microrna family in development and cancer cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3041954/ https://www.ncbi.nlm.nih.gov/pubmed/21224847 http://dx.doi.org/10.1038/emboj.2010.358 |
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