Impact of DLK1-DIO3 imprinted cluster hypomethylation in smoker patients with lung cancer
DNA methylation is important for gene expression and genome stability, and its disruption is thought to play a key role in the initiation and progression of cancer and other diseases. The DLK1-DIO3 cluster has been shown to be imprinted in humans, and some of its components are relevant to diverse p...
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/PMC5796982/ https://www.ncbi.nlm.nih.gov/pubmed/29435111 http://dx.doi.org/10.18632/oncotarget.10611 |
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author | Molina-Pinelo, Sonia Salinas, Ana Moreno-Mata, Nicolás Ferrer, Irene Suarez, Rocío Andrés-León, Eduardo Rodríguez-Paredes, Manuel Gutekunst, Julian Jantus-Lewintre, Eloisa Camps, Carlos Carnero, Amancio Paz-Ares, Luis |
author_facet | Molina-Pinelo, Sonia Salinas, Ana Moreno-Mata, Nicolás Ferrer, Irene Suarez, Rocío Andrés-León, Eduardo Rodríguez-Paredes, Manuel Gutekunst, Julian Jantus-Lewintre, Eloisa Camps, Carlos Carnero, Amancio Paz-Ares, Luis |
author_sort | Molina-Pinelo, Sonia |
collection | PubMed |
description | DNA methylation is important for gene expression and genome stability, and its disruption is thought to play a key role in the initiation and progression of cancer and other diseases. The DLK1-DIO3 cluster has been shown to be imprinted in humans, and some of its components are relevant to diverse pathological processes. The purpose of this study was to assess the methylation patterns of the DLK1-DIO3 cluster in patients with lung cancer to study its relevance in the pathogenesis of this disease. We found a characteristic methylation pattern of this cluster in smoking associated lung cancer, as compared to normal lung tissue. This methylation profile is not patent however in lung cancer of never smokers nor in lung tissue of COPD patients. We found 3 deregulated protein-coding genes at this locus: one was hypermethylated (DIO3) and two were hypomethylated (DLK1 and RTL1). Statistically significant differences were also detected in two different families of SNORDs, two miRNA clusters and four lncRNAs (MEG3, MEG8, MEG9 and LINC00524). These findings were validated using data from the cancer genome atlas (TCGA) database. We have then showed an inverse correlation between DNA methylation and expression levels in 5 randomly selected genes. Several targets of miRNAs included in the DLK1-DIO3 cluster have been experimentally verified as tumor suppressors. All of these results suggest that the dysmethylation of the imprinted DLK1-DIO3 cluster could have a relevant role in the pathogenesis of lung cancer in current and former smokers and may be used for diagnostic and/or therapeutic purposes. |
format | Online Article Text |
id | pubmed-5796982 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-57969822018-02-12 Impact of DLK1-DIO3 imprinted cluster hypomethylation in smoker patients with lung cancer Molina-Pinelo, Sonia Salinas, Ana Moreno-Mata, Nicolás Ferrer, Irene Suarez, Rocío Andrés-León, Eduardo Rodríguez-Paredes, Manuel Gutekunst, Julian Jantus-Lewintre, Eloisa Camps, Carlos Carnero, Amancio Paz-Ares, Luis Oncotarget Research Paper DNA methylation is important for gene expression and genome stability, and its disruption is thought to play a key role in the initiation and progression of cancer and other diseases. The DLK1-DIO3 cluster has been shown to be imprinted in humans, and some of its components are relevant to diverse pathological processes. The purpose of this study was to assess the methylation patterns of the DLK1-DIO3 cluster in patients with lung cancer to study its relevance in the pathogenesis of this disease. We found a characteristic methylation pattern of this cluster in smoking associated lung cancer, as compared to normal lung tissue. This methylation profile is not patent however in lung cancer of never smokers nor in lung tissue of COPD patients. We found 3 deregulated protein-coding genes at this locus: one was hypermethylated (DIO3) and two were hypomethylated (DLK1 and RTL1). Statistically significant differences were also detected in two different families of SNORDs, two miRNA clusters and four lncRNAs (MEG3, MEG8, MEG9 and LINC00524). These findings were validated using data from the cancer genome atlas (TCGA) database. We have then showed an inverse correlation between DNA methylation and expression levels in 5 randomly selected genes. Several targets of miRNAs included in the DLK1-DIO3 cluster have been experimentally verified as tumor suppressors. All of these results suggest that the dysmethylation of the imprinted DLK1-DIO3 cluster could have a relevant role in the pathogenesis of lung cancer in current and former smokers and may be used for diagnostic and/or therapeutic purposes. Impact Journals LLC 2016-07-15 /pmc/articles/PMC5796982/ /pubmed/29435111 http://dx.doi.org/10.18632/oncotarget.10611 Text en Copyright: © 2018 Molina-Pinelo et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Research Paper Molina-Pinelo, Sonia Salinas, Ana Moreno-Mata, Nicolás Ferrer, Irene Suarez, Rocío Andrés-León, Eduardo Rodríguez-Paredes, Manuel Gutekunst, Julian Jantus-Lewintre, Eloisa Camps, Carlos Carnero, Amancio Paz-Ares, Luis Impact of DLK1-DIO3 imprinted cluster hypomethylation in smoker patients with lung cancer |
title | Impact of DLK1-DIO3 imprinted cluster hypomethylation in smoker patients with lung cancer |
title_full | Impact of DLK1-DIO3 imprinted cluster hypomethylation in smoker patients with lung cancer |
title_fullStr | Impact of DLK1-DIO3 imprinted cluster hypomethylation in smoker patients with lung cancer |
title_full_unstemmed | Impact of DLK1-DIO3 imprinted cluster hypomethylation in smoker patients with lung cancer |
title_short | Impact of DLK1-DIO3 imprinted cluster hypomethylation in smoker patients with lung cancer |
title_sort | impact of dlk1-dio3 imprinted cluster hypomethylation in smoker patients with lung cancer |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796982/ https://www.ncbi.nlm.nih.gov/pubmed/29435111 http://dx.doi.org/10.18632/oncotarget.10611 |
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