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Androgen receptor regulates SRC expression through microRNA-203

The SRC kinase has pivotal roles in multiple developmental processes and in tumor progression. An inverse relationship has been observed between androgen receptor (AR) activity and SRC signaling in advanced prostate cancer (PCa); however, the modulation of AR/SRC crosstalk that leads to metastatic P...

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Autores principales: Siu, Man Kit, Chen, Wei-Yu, Tsai, Hong-Yuan, Yeh, Hsiu-Lien, Yin, Juan Juan, Liu, Shih-Yang, Liu, Yen-Nien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5041939/
https://www.ncbi.nlm.nih.gov/pubmed/27028864
http://dx.doi.org/10.18632/oncotarget.8366
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author Siu, Man Kit
Chen, Wei-Yu
Tsai, Hong-Yuan
Yeh, Hsiu-Lien
Yin, Juan Juan
Liu, Shih-Yang
Liu, Yen-Nien
author_facet Siu, Man Kit
Chen, Wei-Yu
Tsai, Hong-Yuan
Yeh, Hsiu-Lien
Yin, Juan Juan
Liu, Shih-Yang
Liu, Yen-Nien
author_sort Siu, Man Kit
collection PubMed
description The SRC kinase has pivotal roles in multiple developmental processes and in tumor progression. An inverse relationship has been observed between androgen receptor (AR) activity and SRC signaling in advanced prostate cancer (PCa); however, the modulation of AR/SRC crosstalk that leads to metastatic PCa is unclear. Here, we showed that patients with high SRC levels displayed correspondingly low canonical AR gene signatures. Our results demonstrated that activated AR induced miR-203 and reduced SRC levels in PCa model systems. miR-203 directly binds to the 3′ UTR of SRC and regulates the stability of SRC mRNA upon AR activation. Moreover, we found that progressive PCa cell migration and growth were associated with a decrease in AR-regulated miR-203 and an increase in SRC. Relationships among AR, miR-203, and SRC were also confirmed in clinical datasets and specimens. We suggest that the induction of SRC results in increased PCa metastasis that is linked to the dysregulation of the AR signaling pathway through the inactivation of miR-203.
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spelling pubmed-50419392016-10-10 Androgen receptor regulates SRC expression through microRNA-203 Siu, Man Kit Chen, Wei-Yu Tsai, Hong-Yuan Yeh, Hsiu-Lien Yin, Juan Juan Liu, Shih-Yang Liu, Yen-Nien Oncotarget Research Paper The SRC kinase has pivotal roles in multiple developmental processes and in tumor progression. An inverse relationship has been observed between androgen receptor (AR) activity and SRC signaling in advanced prostate cancer (PCa); however, the modulation of AR/SRC crosstalk that leads to metastatic PCa is unclear. Here, we showed that patients with high SRC levels displayed correspondingly low canonical AR gene signatures. Our results demonstrated that activated AR induced miR-203 and reduced SRC levels in PCa model systems. miR-203 directly binds to the 3′ UTR of SRC and regulates the stability of SRC mRNA upon AR activation. Moreover, we found that progressive PCa cell migration and growth were associated with a decrease in AR-regulated miR-203 and an increase in SRC. Relationships among AR, miR-203, and SRC were also confirmed in clinical datasets and specimens. We suggest that the induction of SRC results in increased PCa metastasis that is linked to the dysregulation of the AR signaling pathway through the inactivation of miR-203. Impact Journals LLC 2016-03-25 /pmc/articles/PMC5041939/ /pubmed/27028864 http://dx.doi.org/10.18632/oncotarget.8366 Text en Copyright: © 2016 Siu 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
Siu, Man Kit
Chen, Wei-Yu
Tsai, Hong-Yuan
Yeh, Hsiu-Lien
Yin, Juan Juan
Liu, Shih-Yang
Liu, Yen-Nien
Androgen receptor regulates SRC expression through microRNA-203
title Androgen receptor regulates SRC expression through microRNA-203
title_full Androgen receptor regulates SRC expression through microRNA-203
title_fullStr Androgen receptor regulates SRC expression through microRNA-203
title_full_unstemmed Androgen receptor regulates SRC expression through microRNA-203
title_short Androgen receptor regulates SRC expression through microRNA-203
title_sort androgen receptor regulates src expression through microrna-203
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5041939/
https://www.ncbi.nlm.nih.gov/pubmed/27028864
http://dx.doi.org/10.18632/oncotarget.8366
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