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Loss of MEN1 activates DNMT1 implicating DNA hypermethylation as a driver of MEN1 tumorigenesis
Multiple endocrine neoplasia type 1 (MEN1) syndrome results from mutations in the MEN1 gene and causes tumor formation via largely unknown mechanisms. Using a novel genome-wide methylation analysis, we studied tissues from MEN1-parathyroid tumors, Men1 knockout (KO) mice, and Men1 null mouse embryon...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4914310/ https://www.ncbi.nlm.nih.gov/pubmed/26871472 http://dx.doi.org/10.18632/oncotarget.7279 |
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author | Yuan, Ziqiang Claros, Carmen Sánchez Suzuki, Masako Maggi, Elaine C. Kaner, Justin D. Kinstlinger, Noah Gorecka, Jolanta Quinn, Thomas J. Geha, Rula Corn, Amanda Pastoriza, Jessica Jing, Qiang Adem, Asha Wu, Hao Alemu, Girum Du, Yi-Chieh Zheng, Deyou Greally, John M. Libutti, Steven K. |
author_facet | Yuan, Ziqiang Claros, Carmen Sánchez Suzuki, Masako Maggi, Elaine C. Kaner, Justin D. Kinstlinger, Noah Gorecka, Jolanta Quinn, Thomas J. Geha, Rula Corn, Amanda Pastoriza, Jessica Jing, Qiang Adem, Asha Wu, Hao Alemu, Girum Du, Yi-Chieh Zheng, Deyou Greally, John M. Libutti, Steven K. |
author_sort | Yuan, Ziqiang |
collection | PubMed |
description | Multiple endocrine neoplasia type 1 (MEN1) syndrome results from mutations in the MEN1 gene and causes tumor formation via largely unknown mechanisms. Using a novel genome-wide methylation analysis, we studied tissues from MEN1-parathyroid tumors, Men1 knockout (KO) mice, and Men1 null mouse embryonic fibroblast (MEF) cell lines. We demonstrated that inactivation of menin (the protein product of MEN1) increases activity of DNA (cytosine-5)-methyltransferase 1 (DNMT1) by activating retinoblastoma-binding protein 5 (Rbbp5). The increased activity of DNMT1 mediates global DNA hypermethylation, which results in aberrant activation of the Wnt/β-catenin signaling pathway through inactivation of Sox regulatory genes. Our study provides important insights into the role of menin in DNA methylation and its impact on the pathogenesis of MEN1 tumor development. |
format | Online Article Text |
id | pubmed-4914310 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-49143102016-07-11 Loss of MEN1 activates DNMT1 implicating DNA hypermethylation as a driver of MEN1 tumorigenesis Yuan, Ziqiang Claros, Carmen Sánchez Suzuki, Masako Maggi, Elaine C. Kaner, Justin D. Kinstlinger, Noah Gorecka, Jolanta Quinn, Thomas J. Geha, Rula Corn, Amanda Pastoriza, Jessica Jing, Qiang Adem, Asha Wu, Hao Alemu, Girum Du, Yi-Chieh Zheng, Deyou Greally, John M. Libutti, Steven K. Oncotarget Research Paper Multiple endocrine neoplasia type 1 (MEN1) syndrome results from mutations in the MEN1 gene and causes tumor formation via largely unknown mechanisms. Using a novel genome-wide methylation analysis, we studied tissues from MEN1-parathyroid tumors, Men1 knockout (KO) mice, and Men1 null mouse embryonic fibroblast (MEF) cell lines. We demonstrated that inactivation of menin (the protein product of MEN1) increases activity of DNA (cytosine-5)-methyltransferase 1 (DNMT1) by activating retinoblastoma-binding protein 5 (Rbbp5). The increased activity of DNMT1 mediates global DNA hypermethylation, which results in aberrant activation of the Wnt/β-catenin signaling pathway through inactivation of Sox regulatory genes. Our study provides important insights into the role of menin in DNA methylation and its impact on the pathogenesis of MEN1 tumor development. Impact Journals LLC 2016-02-09 /pmc/articles/PMC4914310/ /pubmed/26871472 http://dx.doi.org/10.18632/oncotarget.7279 Text en Copyright: © 2016 Yuan 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 Yuan, Ziqiang Claros, Carmen Sánchez Suzuki, Masako Maggi, Elaine C. Kaner, Justin D. Kinstlinger, Noah Gorecka, Jolanta Quinn, Thomas J. Geha, Rula Corn, Amanda Pastoriza, Jessica Jing, Qiang Adem, Asha Wu, Hao Alemu, Girum Du, Yi-Chieh Zheng, Deyou Greally, John M. Libutti, Steven K. Loss of MEN1 activates DNMT1 implicating DNA hypermethylation as a driver of MEN1 tumorigenesis |
title | Loss of MEN1 activates DNMT1 implicating DNA hypermethylation as a driver of MEN1 tumorigenesis |
title_full | Loss of MEN1 activates DNMT1 implicating DNA hypermethylation as a driver of MEN1 tumorigenesis |
title_fullStr | Loss of MEN1 activates DNMT1 implicating DNA hypermethylation as a driver of MEN1 tumorigenesis |
title_full_unstemmed | Loss of MEN1 activates DNMT1 implicating DNA hypermethylation as a driver of MEN1 tumorigenesis |
title_short | Loss of MEN1 activates DNMT1 implicating DNA hypermethylation as a driver of MEN1 tumorigenesis |
title_sort | loss of men1 activates dnmt1 implicating dna hypermethylation as a driver of men1 tumorigenesis |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4914310/ https://www.ncbi.nlm.nih.gov/pubmed/26871472 http://dx.doi.org/10.18632/oncotarget.7279 |
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