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MicroRNA-141 suppresses prostate cancer stem cells and metastasis by targeting a cohort of pro-metastasis genes
MicroRNAs play important roles in regulating tumour development, progression and metastasis. Here we show that one of the miR-200 family members, miR-141, is under-expressed in several prostate cancer (PCa) stem/progenitor cell populations in both xenograft and primary patient tumours. Enforced expr...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5264244/ https://www.ncbi.nlm.nih.gov/pubmed/28112170 http://dx.doi.org/10.1038/ncomms14270 |
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author | Liu, Can Liu, Ruifang Zhang, Dingxiao Deng, Qu Liu, Bigang Chao, Hsueh-Ping Rycaj, Kiera Takata, Yoko Lin, Kevin Lu, Yue Zhong, Yi Krolewski, John Shen, Jianjun Tang, Dean G. |
author_facet | Liu, Can Liu, Ruifang Zhang, Dingxiao Deng, Qu Liu, Bigang Chao, Hsueh-Ping Rycaj, Kiera Takata, Yoko Lin, Kevin Lu, Yue Zhong, Yi Krolewski, John Shen, Jianjun Tang, Dean G. |
author_sort | Liu, Can |
collection | PubMed |
description | MicroRNAs play important roles in regulating tumour development, progression and metastasis. Here we show that one of the miR-200 family members, miR-141, is under-expressed in several prostate cancer (PCa) stem/progenitor cell populations in both xenograft and primary patient tumours. Enforced expression of miR-141 in CD44(+) and bulk PCa cells inhibits cancer stem cell properties including holoclone and sphere formation, as well as invasion, and suppresses tumour regeneration and metastasis. Moreover, miR-141 expression enforces a strong epithelial phenotype with a partial loss of mesenchymal phenotype. Whole-genome RNA sequencing uncovers novel miR-141-regulated molecular targets in PCa cells including the Rho GTPase family members (for example, CDC42, CDC42EP3, RAC1 and ARPC5) and stem cell molecules CD44 and EZH2, all of which are validated as direct and functionally relevant targets of miR-141. Our results suggest that miR-141 employs multiple mechanisms to obstruct tumour growth and metastasis. |
format | Online Article Text |
id | pubmed-5264244 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-52642442017-02-03 MicroRNA-141 suppresses prostate cancer stem cells and metastasis by targeting a cohort of pro-metastasis genes Liu, Can Liu, Ruifang Zhang, Dingxiao Deng, Qu Liu, Bigang Chao, Hsueh-Ping Rycaj, Kiera Takata, Yoko Lin, Kevin Lu, Yue Zhong, Yi Krolewski, John Shen, Jianjun Tang, Dean G. Nat Commun Article MicroRNAs play important roles in regulating tumour development, progression and metastasis. Here we show that one of the miR-200 family members, miR-141, is under-expressed in several prostate cancer (PCa) stem/progenitor cell populations in both xenograft and primary patient tumours. Enforced expression of miR-141 in CD44(+) and bulk PCa cells inhibits cancer stem cell properties including holoclone and sphere formation, as well as invasion, and suppresses tumour regeneration and metastasis. Moreover, miR-141 expression enforces a strong epithelial phenotype with a partial loss of mesenchymal phenotype. Whole-genome RNA sequencing uncovers novel miR-141-regulated molecular targets in PCa cells including the Rho GTPase family members (for example, CDC42, CDC42EP3, RAC1 and ARPC5) and stem cell molecules CD44 and EZH2, all of which are validated as direct and functionally relevant targets of miR-141. Our results suggest that miR-141 employs multiple mechanisms to obstruct tumour growth and metastasis. Nature Publishing Group 2017-01-23 /pmc/articles/PMC5264244/ /pubmed/28112170 http://dx.doi.org/10.1038/ncomms14270 Text en Copyright © 2017, The Author(s) 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 Liu, Can Liu, Ruifang Zhang, Dingxiao Deng, Qu Liu, Bigang Chao, Hsueh-Ping Rycaj, Kiera Takata, Yoko Lin, Kevin Lu, Yue Zhong, Yi Krolewski, John Shen, Jianjun Tang, Dean G. MicroRNA-141 suppresses prostate cancer stem cells and metastasis by targeting a cohort of pro-metastasis genes |
title | MicroRNA-141 suppresses prostate cancer stem cells and metastasis by targeting a cohort of pro-metastasis genes |
title_full | MicroRNA-141 suppresses prostate cancer stem cells and metastasis by targeting a cohort of pro-metastasis genes |
title_fullStr | MicroRNA-141 suppresses prostate cancer stem cells and metastasis by targeting a cohort of pro-metastasis genes |
title_full_unstemmed | MicroRNA-141 suppresses prostate cancer stem cells and metastasis by targeting a cohort of pro-metastasis genes |
title_short | MicroRNA-141 suppresses prostate cancer stem cells and metastasis by targeting a cohort of pro-metastasis genes |
title_sort | microrna-141 suppresses prostate cancer stem cells and metastasis by targeting a cohort of pro-metastasis genes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5264244/ https://www.ncbi.nlm.nih.gov/pubmed/28112170 http://dx.doi.org/10.1038/ncomms14270 |
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