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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
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.
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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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