ArticleCancer research2010
Aberrant DNA methylation links cancer susceptibility locus 15q25.1 to apoptotic regulation and lung cancer.
Article in Cancer research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Association between two CHRNA3 variants and susceptibility of lung cancer: a meta-analysis.Scientific reports · 2016Pooled it
- Dietary supplementation with polyunsaturated fatty acid during pregnancy modulates DNA methylation at IGF2/H19 imprinted genes and growth of infants.Physiological genomics · 2014Trial
- Modulation of DNA methylation states and infant immune system by dietary supplementation with ω-3 PUFA during pregnancy in an intervention study.The American journal of clinical nutrition · 2013Trial
- Functional studies of lung cancer GWAS beyond association.Human molecular genetics · 2022Review
- Umbrella Review on Associations Between Single Nucleotide Polymorphisms and Lung Cancer Risk.Frontiers in molecular biosciences · 2021Review
- αO-Conotoxin GeXIVA Inhibits the Growth of Breast Cancer Cells via Interaction with α9 Nicotine Acetylcholine Receptors.Marine drugs · 2020Article
- Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk.Nature communications · 2018Article
- Understanding the role of the chromosome 15q25.1 in COPD through epigenetics and transcriptomics.European journal of human genetics : EJHG · 2018Article
- Expression patterns for nicotinic acetylcholine receptor subunit genes in smoking-related lung cancers.Oncotarget · 2017Article
- Nicotine facilitates VSMC dysfunction through a miR-200b/RhoGDIA/cytoskeleton module.Scientific reports · 2017Article
- Nicotinic Acetylcholine Receptor Subtype Alpha-9 Mediates Triple-Negative Breast Cancers Based on a Spontaneous Pulmonary Metastasis Mouse Model.Frontiers in cellular neuroscience · 2017Article
- Nicotinic cholinergic receptors in esophagus: Early alteration during carcinogenesis and prognostic value.World journal of gastroenterology · 2016Article
- Nicotinic acetylcholine receptors and cancer.Biomedical reports · 2016Article
- The Oncogenic Functions of Nicotinic Acetylcholine Receptors.Journal of oncology · 2016Review
- A multiancestry study identifies novel genetic associations with CHRNA5 methylation in human brain and risk of nicotine dependence.Human molecular genetics · 2015Article
- Nicotinic receptors in non-human primates: Analysis of genetic and functional conservation with humans.Neuropharmacology · 2015Review
- Acetylcholine receptor pathway in lung cancer: New twists to an old story.World journal of clinical oncology · 2014Review
- Optimized DNA extraction from neonatal dried blood spots: application in methylome profiling.BMC biotechnology · 2014Article
- Functional characterization of SNPs in CHRNA3/B4 intergenic region associated with drug behaviors.Brain research · 2013Article
- Epigenetic screen identifies genotype-specific promoter DNA methylation and oncogenic potential of CHRNB4.Oncogene · 2013Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Nicotinic acetylcholine receptor (nAChR) genes form a highly conserved gene cluster at the lung cancer susceptibility locus 15q25.1. In this study, we show that the CHRNalpha3 gene encoding the nAChRalpha3 subunit is a frequent target of aberrant DNA hypermethylation and silencing in lung cancer, whereas the adjacent CHRNbeta4 and CHRNalpha5 genes exhibit moderate and no methylation, respectively. Treatment of cancer cells exhibiting CHRNalpha3 hypermethylation with DNA methylation inhibitors caused demethylation of the CHRNalpha3 promoter and gene reactivation. Restoring CHRNalpha3 levels through ectopic expression induced apoptotic cell death. Small hairpin RNA-mediated depletion of nAChRalpha3 in CHRNalpha3-expressing lung cancer cells elicited a dramatic Ca(2+) influx response in the presence of nicotine, followed by activation of the Akt survival pathway. CHRNalpha3-depleted cells were resistant to apoptosis-inducing agents, underscoring the importance of epigenetic silencing of the CHRNalpha3 gene in human cancer. In defining a mechanism of epigenetic control of nAChR expression in nonneuronal tissues, our findings offer a functional link between susceptibility locus 15q25.1 and lung cancer, and suggest nAChRs to be theranostic targets for cancer detection and chemoprevention.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.