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Dysregulation of p53-RBM25-mediated circAMOTL1L biogenesis contributes to prostate cancer progression through the circAMOTL1L-miR-193a-5p-Pcdha pathway

p53, circRNAs and miRNAs are important components of the regulatory network that activates the EMT program in cancer metastasis. In prostate cancer (PCa), however, it has not been investigated whether and how p53 regulates EMT by circRNAs and miRNAs. Here we show that a Amotl1-derived circRNA, terme...

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Autores principales: Yang, Zhan, Qu, Chang-Bao, Zhang, Yong, Zhang, Wen-Feng, Wang, Dan-Dan, Gao, Chun-Cheng, Ma, Long, Chen, Jin-Suo, Liu, Kai-Long, Zheng, Bin, Zhang, Xin-Hua, Zhang, Man-Li, Wang, Xiao-Lu, Wen, Jin-Kun, Li, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484770/
https://www.ncbi.nlm.nih.gov/pubmed/30531834
http://dx.doi.org/10.1038/s41388-018-0602-8
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author Yang, Zhan
Qu, Chang-Bao
Zhang, Yong
Zhang, Wen-Feng
Wang, Dan-Dan
Gao, Chun-Cheng
Ma, Long
Chen, Jin-Suo
Liu, Kai-Long
Zheng, Bin
Zhang, Xin-Hua
Zhang, Man-Li
Wang, Xiao-Lu
Wen, Jin-Kun
Li, Wei
author_facet Yang, Zhan
Qu, Chang-Bao
Zhang, Yong
Zhang, Wen-Feng
Wang, Dan-Dan
Gao, Chun-Cheng
Ma, Long
Chen, Jin-Suo
Liu, Kai-Long
Zheng, Bin
Zhang, Xin-Hua
Zhang, Man-Li
Wang, Xiao-Lu
Wen, Jin-Kun
Li, Wei
author_sort Yang, Zhan
collection PubMed
description p53, circRNAs and miRNAs are important components of the regulatory network that activates the EMT program in cancer metastasis. In prostate cancer (PCa), however, it has not been investigated whether and how p53 regulates EMT by circRNAs and miRNAs. Here we show that a Amotl1-derived circRNA, termed circAMOTL1L, is downregulated in human PCa, and that decreased circAMOTL1L facilitates PCa cell migration and invasion through downregulating E-cadherin and upregulating vimentin, thus leading to EMT and PCa progression. Mechanistically, we demonstrate that circAMOTL1L serves as a sponge for binding miR-193a-5p in PCa cells, relieving miR-193a-5p repression of Pcdha gene cluster (a subset of the cadherin superfamily members). Accordingly, dysregulation of the circAMOTL1L-miR-193a-5p-Pcdha8 regulatory pathway mediated by circAMOTL1L downregulation contributes to PCa growth in vivo. Further, we show that RBM25 binds directly to circAMOTL1L and induces its biogenesis, whereas p53 regulates EMT via direct activation of RBM25 gene. These findings have linked p53/RBM25-mediated circAMOTL1L-miR-193a-5p-Pcdha regulatory axis to EMT in metastatic progression of PCa. Targeting this newly identified regulatory axis provides a potential therapeutic strategy for aggressive PCa.
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spelling pubmed-64847702019-06-25 Dysregulation of p53-RBM25-mediated circAMOTL1L biogenesis contributes to prostate cancer progression through the circAMOTL1L-miR-193a-5p-Pcdha pathway Yang, Zhan Qu, Chang-Bao Zhang, Yong Zhang, Wen-Feng Wang, Dan-Dan Gao, Chun-Cheng Ma, Long Chen, Jin-Suo Liu, Kai-Long Zheng, Bin Zhang, Xin-Hua Zhang, Man-Li Wang, Xiao-Lu Wen, Jin-Kun Li, Wei Oncogene Article p53, circRNAs and miRNAs are important components of the regulatory network that activates the EMT program in cancer metastasis. In prostate cancer (PCa), however, it has not been investigated whether and how p53 regulates EMT by circRNAs and miRNAs. Here we show that a Amotl1-derived circRNA, termed circAMOTL1L, is downregulated in human PCa, and that decreased circAMOTL1L facilitates PCa cell migration and invasion through downregulating E-cadherin and upregulating vimentin, thus leading to EMT and PCa progression. Mechanistically, we demonstrate that circAMOTL1L serves as a sponge for binding miR-193a-5p in PCa cells, relieving miR-193a-5p repression of Pcdha gene cluster (a subset of the cadherin superfamily members). Accordingly, dysregulation of the circAMOTL1L-miR-193a-5p-Pcdha8 regulatory pathway mediated by circAMOTL1L downregulation contributes to PCa growth in vivo. Further, we show that RBM25 binds directly to circAMOTL1L and induces its biogenesis, whereas p53 regulates EMT via direct activation of RBM25 gene. These findings have linked p53/RBM25-mediated circAMOTL1L-miR-193a-5p-Pcdha regulatory axis to EMT in metastatic progression of PCa. Targeting this newly identified regulatory axis provides a potential therapeutic strategy for aggressive PCa. Nature Publishing Group UK 2018-12-07 2019 /pmc/articles/PMC6484770/ /pubmed/30531834 http://dx.doi.org/10.1038/s41388-018-0602-8 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Yang, Zhan
Qu, Chang-Bao
Zhang, Yong
Zhang, Wen-Feng
Wang, Dan-Dan
Gao, Chun-Cheng
Ma, Long
Chen, Jin-Suo
Liu, Kai-Long
Zheng, Bin
Zhang, Xin-Hua
Zhang, Man-Li
Wang, Xiao-Lu
Wen, Jin-Kun
Li, Wei
Dysregulation of p53-RBM25-mediated circAMOTL1L biogenesis contributes to prostate cancer progression through the circAMOTL1L-miR-193a-5p-Pcdha pathway
title Dysregulation of p53-RBM25-mediated circAMOTL1L biogenesis contributes to prostate cancer progression through the circAMOTL1L-miR-193a-5p-Pcdha pathway
title_full Dysregulation of p53-RBM25-mediated circAMOTL1L biogenesis contributes to prostate cancer progression through the circAMOTL1L-miR-193a-5p-Pcdha pathway
title_fullStr Dysregulation of p53-RBM25-mediated circAMOTL1L biogenesis contributes to prostate cancer progression through the circAMOTL1L-miR-193a-5p-Pcdha pathway
title_full_unstemmed Dysregulation of p53-RBM25-mediated circAMOTL1L biogenesis contributes to prostate cancer progression through the circAMOTL1L-miR-193a-5p-Pcdha pathway
title_short Dysregulation of p53-RBM25-mediated circAMOTL1L biogenesis contributes to prostate cancer progression through the circAMOTL1L-miR-193a-5p-Pcdha pathway
title_sort dysregulation of p53-rbm25-mediated circamotl1l biogenesis contributes to prostate cancer progression through the circamotl1l-mir-193a-5p-pcdha pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484770/
https://www.ncbi.nlm.nih.gov/pubmed/30531834
http://dx.doi.org/10.1038/s41388-018-0602-8
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