RT Journal Article
T1 Impact of DLK1-DIO3 imprinted cluster hypomethylation in smoker patients with lung cancer.
A1 Molina-Pinelo, Sonia
A1 Salinas, Ana
A1 Moreno-Mata, Nicolás
A1 Ferrer, Irene
A1 Suarez, Rocío
A1 Andrés-León, Eduardo
A1 Rodríguez-Paredes, Manuel
A1 Gutekunst, Julian
A1 Jantus-Lewintre, Eloisa
A1 Camps, Carlos
A1 Carnero, Amancio
A1 Paz-Ares, Luis
K1 COPD
K1 DLK1-DIO3 cluster
K1 epigenetic
K1 lung cancer
K1 transcriptional regulation
AB 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.
YR 2016
FD 2016-07-15
LK https://hdl.handle.net/10668/25124
UL https://hdl.handle.net/10668/25124
LA en
DS RISalud
RD Apr 17, 2025