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Dysregulation of miRNAs-COUP-TFII-FOXM1-CENPF axis contributes to the metastasis of prostate cancer

Although early detection and treatment of prostate cancer (PCa) improves outcomes, many patients still die of metastatic PCa. Here, we report that metastatic PCa exhibits reduced levels of the microRNAsmiR-101 and miR-27a. These micro-RNAs (miRNAs) negatively regulate cell invasion and inhibit the e...

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Autores principales: Lin, Shih-Chieh, Kao, Chung-Yang, Lee, Hui-Ju, Creighton, Chad J., Ittmann, Michael M., Tsai, Shaw-Jenq, Tsai, Sophia Y., Tsai, Ming-Jer
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848536/
https://www.ncbi.nlm.nih.gov/pubmed/27108958
http://dx.doi.org/10.1038/ncomms11418
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author Lin, Shih-Chieh
Kao, Chung-Yang
Lee, Hui-Ju
Creighton, Chad J.
Ittmann, Michael M.
Tsai, Shaw-Jenq
Tsai, Sophia Y.
Tsai, Ming-Jer
author_facet Lin, Shih-Chieh
Kao, Chung-Yang
Lee, Hui-Ju
Creighton, Chad J.
Ittmann, Michael M.
Tsai, Shaw-Jenq
Tsai, Sophia Y.
Tsai, Ming-Jer
author_sort Lin, Shih-Chieh
collection PubMed
description Although early detection and treatment of prostate cancer (PCa) improves outcomes, many patients still die of metastatic PCa. Here, we report that metastatic PCa exhibits reduced levels of the microRNAsmiR-101 and miR-27a. These micro-RNAs (miRNAs) negatively regulate cell invasion and inhibit the expression of FOXM1 and CENPF, two master regulators of metastasis in PCa. Interestingly, the repression of FOXM1 and CENPF by these miRNAs occurs through COUP-TFII, a member of the orphan nuclear receptors family. Loss of miR-101 positively correlates with the increase of COUP-TFII-FOXM1-CENPF activity in clinical PCa data sets, implicating clinical relevance of such regulation. Further studies show that COUP-TFII is a critical factor controlling metastatic gene networks to promote PCa metastasis. Most importantly, this miRNA-COUP-TFII-FOXM1-CENPF regulatory axis is also involved in the development of enzalutaminde resistance. Taken together, our findings highlight the contribution of specific miRNAs through the regulation of the COUP-TFII-FOXM1-CENPF cascade in PCa metastasis and drug resistance.
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spelling pubmed-48485362016-05-05 Dysregulation of miRNAs-COUP-TFII-FOXM1-CENPF axis contributes to the metastasis of prostate cancer Lin, Shih-Chieh Kao, Chung-Yang Lee, Hui-Ju Creighton, Chad J. Ittmann, Michael M. Tsai, Shaw-Jenq Tsai, Sophia Y. Tsai, Ming-Jer Nat Commun Article Although early detection and treatment of prostate cancer (PCa) improves outcomes, many patients still die of metastatic PCa. Here, we report that metastatic PCa exhibits reduced levels of the microRNAsmiR-101 and miR-27a. These micro-RNAs (miRNAs) negatively regulate cell invasion and inhibit the expression of FOXM1 and CENPF, two master regulators of metastasis in PCa. Interestingly, the repression of FOXM1 and CENPF by these miRNAs occurs through COUP-TFII, a member of the orphan nuclear receptors family. Loss of miR-101 positively correlates with the increase of COUP-TFII-FOXM1-CENPF activity in clinical PCa data sets, implicating clinical relevance of such regulation. Further studies show that COUP-TFII is a critical factor controlling metastatic gene networks to promote PCa metastasis. Most importantly, this miRNA-COUP-TFII-FOXM1-CENPF regulatory axis is also involved in the development of enzalutaminde resistance. Taken together, our findings highlight the contribution of specific miRNAs through the regulation of the COUP-TFII-FOXM1-CENPF cascade in PCa metastasis and drug resistance. Nature Publishing Group 2016-04-25 /pmc/articles/PMC4848536/ /pubmed/27108958 http://dx.doi.org/10.1038/ncomms11418 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. 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
Lin, Shih-Chieh
Kao, Chung-Yang
Lee, Hui-Ju
Creighton, Chad J.
Ittmann, Michael M.
Tsai, Shaw-Jenq
Tsai, Sophia Y.
Tsai, Ming-Jer
Dysregulation of miRNAs-COUP-TFII-FOXM1-CENPF axis contributes to the metastasis of prostate cancer
title Dysregulation of miRNAs-COUP-TFII-FOXM1-CENPF axis contributes to the metastasis of prostate cancer
title_full Dysregulation of miRNAs-COUP-TFII-FOXM1-CENPF axis contributes to the metastasis of prostate cancer
title_fullStr Dysregulation of miRNAs-COUP-TFII-FOXM1-CENPF axis contributes to the metastasis of prostate cancer
title_full_unstemmed Dysregulation of miRNAs-COUP-TFII-FOXM1-CENPF axis contributes to the metastasis of prostate cancer
title_short Dysregulation of miRNAs-COUP-TFII-FOXM1-CENPF axis contributes to the metastasis of prostate cancer
title_sort dysregulation of mirnas-coup-tfii-foxm1-cenpf axis contributes to the metastasis of prostate cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848536/
https://www.ncbi.nlm.nih.gov/pubmed/27108958
http://dx.doi.org/10.1038/ncomms11418
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