ArticleJournal of cellular and molecular medicine2010
Aberrant methylation and associated transcriptional mobilization of Alu elements contributes to genomic instability in hypoxia.
Article in Journal of cellular and molecular medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 44 citations in OpenAlex.
- Integrative Transcriptomic Analysis Identifies Hypoxia-responsive Cell Cycle Hub Genes as Prognostic Markers in Glioblastoma.Annals of neurosciences · 2026Article
- DNA methylation heterogeneity in complex tumor microenvironment: Quantitative methods, influencing factors, and clinical implications.Genes & diseases · 2026Review
- LINE-1 hypomethylation in cell-free DNA of high-grade glioma patients correlates with tissue levels and is associated with reduced DNMT1 and H4K20me3 expression.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Comparative DNA methylation reveals epigenetic adaptation to high altitude in snub-nosed monkeys.Zoological research · 2024Article
- Tumor suppressor genes are differentially regulated with dietary folate modulations in a rat model of hepatocellular carcinoma.Molecular and cellular biochemistry · 2021Article
- DNA methylation of individual repetitive elements in hepatitis C virus infection-induced hepatocellular carcinoma.Clinical epigenetics · 2019Article
- Article
- Scriptaid overcomes hypoxia-induced cisplatin resistance in both wild-type and mutant p53 lung cancer cells.Oncotarget · 2016Article
- MBD3 mediates epigenetic regulation on EPAS1 promoter in cancer.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Review
- 5-Hydroxymethylcytosine-mediated alteration of transposon activity associated with the exposure to adverse in utero environments in human.Human molecular genetics · 2016Article
- Epigenetics, TET proteins, and hypoxia in epithelial-mesenchymal transition and tumorigenesis.BioMedicine · 2016Article
- Hypoxia, Epithelial-Mesenchymal Transition, and TET-Mediated Epigenetic Changes.Journal of clinical medicine · 2016Review
- The potential role of Alu Y in the development of resistance to SN38 (Irinotecan) or oxaliplatin in colorectal cancer.BMC genomics · 2015Article
- A gene expression signature identifying transient DNMT1 depletion as a causal factor of cancer-germline gene activation in melanoma.Clinical epigenetics · 2015Article
- Extracellular vesicles shed by glioma cells: pathogenic role and clinical value.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Review
- Dynamic Alu methylation during normal development, aging, and tumorigenesis.BioMed research international · 2014Review
- Real-time dynamics of methyl-CpG-binding domain protein 3 and its role in DNA demethylation by fluorescence correlation spectroscopy.Epigenetics · 2013Article
- HERV-K and LINE-1 DNA Methylation and Reexpression in Urothelial Carcinoma.Frontiers in oncology · 2013Article
- Suffocating cancer: hypoxia-associated epimutations as targets for cancer therapy.Clinical epigenetics · 2011Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia is an integral part of tumorigenesis and contributes extensively to the neoplastic phenotype including drug resistance and genomic instability. It has also been reported that hypoxia results in global demethylation. Because a majority of the cytosine-phosphate-guanine (CpG) islands are found within the repeat elements of DNA, and are usually methylated under normoxic conditions, we suggested that retrotransposable Alu or short interspersed nuclear elements (SINEs) which show altered methylation and associated changes of gene expression during hypoxia, could be associated with genomic instability. U87MG glioblastoma cells were cultured in 0.1% O₂ for 6 weeks and compared with cells cultured in 21% O₂ for the same duration. Real-time PCR analysis showed a significant increase in SINE and reverse transcriptase coding long interspersed nuclear element (LINE) transcripts during hypoxia. Sequencing of bisulphite treated DNA as well as the Combined Bisulfite Restriction Analysis (COBRA) assay showed that the SINE loci studied underwent significant hypomethylation though there was patchy hypermethylation at a few sites. The inter-alu PCR profile of DNA from cells cultured under 6-week hypoxia, its 4-week revert back to normoxia and 6-week normoxia showed several changes in the band pattern indicating increased alu mediated genomic alteration. Our results show that aberrant methylation leading to increased transcription of SINE and reverse transcriptase associated LINE elements could lead to increased genomic instability in hypoxia. This might be a cause of genetic heterogeneity in tumours especially in variegated hypoxic environment and lead to a development of foci of more aggressive tumour cells.
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