2026-06-14T03:31:57Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/105402024-11-29T17:16:58Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Molina-Pinelo, Sonia author Salinas, Ana author Moreno-Mata, Nicolás author Ferrer, Irene author Suarez, Rocío author Andrés-León, Eduardo author Rodríguez-Paredes, Manuel author Gutekunst, Julian author Jantus-Lewintre, Eloisa author Camps, Carlos author Carnero, Amancio author Paz Ares, Luis Gonzaga author 2018-01-12 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. Oncotarget. 2016;9(4):4395-4410. 10.18632/oncotarget.10611 1949-2553 Oncotarget 29435111 http://hdl.handle.net/20.500.12105/10540 Lung cancer Epigenetic DLK1-DIO3 cluster Transcriptional regulation COPD Impact of DLK1-DIO3 imprinted cluster hypomethylation in smoker patients with lung cancer