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Manipulation of prostate cancer metastasis by locus-specific modification of the CRMP4 promoter region using chimeric TALE DNA methyltransferase and demethylase
Prostate cancer is the most commonly diagnosed non-cutaneous cancer and one of the leading causes of cancer death for North American men. Whereas localized prostate cancer can be cured, there is currently no cure for metastatic prostate cancer. Here we report a novel approach that utilizes designed...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496338/ https://www.ncbi.nlm.nih.gov/pubmed/25888628 |
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author | Li, Ke Pang, Jun Cheng, Huaiyan Liu, Wei-Peng Di, Jin-Ming Xiao, Heng-Jun Luo, Yun Zhang, Hao Huang, Wen-Tao Chen, Ming-Kun Li, Liao-Yuan Shao, Chun-Kui Feng, Ying-Hong Gao, Xin |
author_facet | Li, Ke Pang, Jun Cheng, Huaiyan Liu, Wei-Peng Di, Jin-Ming Xiao, Heng-Jun Luo, Yun Zhang, Hao Huang, Wen-Tao Chen, Ming-Kun Li, Liao-Yuan Shao, Chun-Kui Feng, Ying-Hong Gao, Xin |
author_sort | Li, Ke |
collection | PubMed |
description | Prostate cancer is the most commonly diagnosed non-cutaneous cancer and one of the leading causes of cancer death for North American men. Whereas localized prostate cancer can be cured, there is currently no cure for metastatic prostate cancer. Here we report a novel approach that utilizes designed chimeric transcription activator-like effectors (dTALEs) to control prostate cancer metastasis. Transfection of dTALEs of DNA methyltransferase or demethylase induced artificial, yet active locus-specific CpG and subsequent histone modifications. These manipulations markedly altered expression of endogenous CRMP4, a metastasis suppressor gene. Remarkably, locus-specific CpG demethylation of the CRMP4 promoter in metastatic PC3 cells abolished metastasis, whereas locus-specific CpG methylation of the promoter in non-metastatic 22Rv1 cells induced metastasis. CRMP4-mediated metastasis suppression was found to require activation of Akt/Rac1 signaling and down-regulation of MMP-9 expression. This proof-of-concept study with dTALEs for locus-specific epigenomic manipulation validates the selected CpG methylation of CRMP4 gene as an independent biomarker for diagnosis and prognosis of prostate cancer metastasis and opens up a novel avenue for mechanistic research on cancer biology. |
format | Online Article Text |
id | pubmed-4496338 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-44963382015-07-15 Manipulation of prostate cancer metastasis by locus-specific modification of the CRMP4 promoter region using chimeric TALE DNA methyltransferase and demethylase Li, Ke Pang, Jun Cheng, Huaiyan Liu, Wei-Peng Di, Jin-Ming Xiao, Heng-Jun Luo, Yun Zhang, Hao Huang, Wen-Tao Chen, Ming-Kun Li, Liao-Yuan Shao, Chun-Kui Feng, Ying-Hong Gao, Xin Oncotarget Research Paper Prostate cancer is the most commonly diagnosed non-cutaneous cancer and one of the leading causes of cancer death for North American men. Whereas localized prostate cancer can be cured, there is currently no cure for metastatic prostate cancer. Here we report a novel approach that utilizes designed chimeric transcription activator-like effectors (dTALEs) to control prostate cancer metastasis. Transfection of dTALEs of DNA methyltransferase or demethylase induced artificial, yet active locus-specific CpG and subsequent histone modifications. These manipulations markedly altered expression of endogenous CRMP4, a metastasis suppressor gene. Remarkably, locus-specific CpG demethylation of the CRMP4 promoter in metastatic PC3 cells abolished metastasis, whereas locus-specific CpG methylation of the promoter in non-metastatic 22Rv1 cells induced metastasis. CRMP4-mediated metastasis suppression was found to require activation of Akt/Rac1 signaling and down-regulation of MMP-9 expression. This proof-of-concept study with dTALEs for locus-specific epigenomic manipulation validates the selected CpG methylation of CRMP4 gene as an independent biomarker for diagnosis and prognosis of prostate cancer metastasis and opens up a novel avenue for mechanistic research on cancer biology. Impact Journals LLC 2015-04-09 /pmc/articles/PMC4496338/ /pubmed/25888628 Text en Copyright: © 2015 Li 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 Li, Ke Pang, Jun Cheng, Huaiyan Liu, Wei-Peng Di, Jin-Ming Xiao, Heng-Jun Luo, Yun Zhang, Hao Huang, Wen-Tao Chen, Ming-Kun Li, Liao-Yuan Shao, Chun-Kui Feng, Ying-Hong Gao, Xin Manipulation of prostate cancer metastasis by locus-specific modification of the CRMP4 promoter region using chimeric TALE DNA methyltransferase and demethylase |
title | Manipulation of prostate cancer metastasis by locus-specific modification of the CRMP4 promoter region using chimeric TALE DNA methyltransferase and demethylase |
title_full | Manipulation of prostate cancer metastasis by locus-specific modification of the CRMP4 promoter region using chimeric TALE DNA methyltransferase and demethylase |
title_fullStr | Manipulation of prostate cancer metastasis by locus-specific modification of the CRMP4 promoter region using chimeric TALE DNA methyltransferase and demethylase |
title_full_unstemmed | Manipulation of prostate cancer metastasis by locus-specific modification of the CRMP4 promoter region using chimeric TALE DNA methyltransferase and demethylase |
title_short | Manipulation of prostate cancer metastasis by locus-specific modification of the CRMP4 promoter region using chimeric TALE DNA methyltransferase and demethylase |
title_sort | manipulation of prostate cancer metastasis by locus-specific modification of the crmp4 promoter region using chimeric tale dna methyltransferase and demethylase |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496338/ https://www.ncbi.nlm.nih.gov/pubmed/25888628 |
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