Long interspersed nuclear element-1 hypomethylation in cancer: biology and clinical applications
Open accessAbstract
UNLABELLED: Epigenetic changes in long interspersed nuclear element-1s (LINE-1s or L1s) occur early during the process of carcinogenesis. A lower methylation level (hypomethylation) of LINE-1 is common in most cancers, and the methylation level is further decreased in more advanced cancers. Consequently, several previous studies have suggested the use of LINE-1 hypomethylation levels in cancer screening, risk assessment, tumor staging, and prognostic prediction. Epigenomic changes are complex, and global hypomethylation influences LINE-1s in a generalized fashion. However, the methylation levels of some loci are dependent on their locations. The consequences of LINE-1 hypomethylation are genomic instability and alteration of gene expression. There are several mechanisms that promote both of these consequences in cis. Therefore, the methylation levels of different sets of LINE-1s may represent certain phenotypes. Furthermore, the methylation levels of specific sets of LINE-1s may indicate carcinogenesis-dependent hypomethylation. LINE-1 methylation pattern analysis can classify LINE-1s into one of three classes based on the number of methylated CpG dinucleotides. These classes include hypermethylation, partial methylation, and hypomethylation. The number of partial and hypermethylated loci, but not hypomethylated LINE-1s, is different among normal cell types. Consequently, the number of hypomethylated loci is a more promising marker than methylation level in the detection of cancer DNA. Further genome-wide studies to measure the methylation level of each LINE-1 locus may improve PCR-based methylation analysis to allow for a more specific and sensitive detection of cancer DNA or for an analysis of certain cancer phenotypes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13148-011-0032-8) contains supplementary material, which is available to authorized users.
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L1s are activated by loss of DNA methylation, which often occurs during premalignant hyperplasia; the resulting IFN-I response could then trigger cell death pathways.
“L1s are activated by loss of DNA methylation, which often occurs during premalignant hyperplasia125; the resulting IFN-I response could then trigger cell death pathways.”
From The role of retrotransposable elements in ageing and age-associated diseases (2021) · cites this paper as [125]
The section “LINE-1 methylation regulates gene expression in cis” (page unavailable) says LINE-1 transcriptional activity correlates with hypomethylation. “LINE-1 and other IRS methylation levels in cancer” reports hypomethylation in certain premalignant lesions, but does not establish that it often occurs during premalignant hyperplasia; it also reports hypermethylation in some lesions. The IFN-I and cell-death clause follows the citation and is not attributed to this source. (LLM, conf=0.87)
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Argonaute 4 as an Effector Protein in RNA-Directed DNA Methylation in Human Cells
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Genes associated with the cis-regulatory functions of intragenic LINE-1 elements
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Self-citationLINE-1 and Alu Methylation Patterns in Lymph Node Metastases of Head and Neck Cancers
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Kalayasiri, R., Kraijak, K., Mutirangura, A., & Maes, M. H. J. (2019) · Schizophrenia Research · doi:10.1016/j.schres.2019.02.015 · Cited by 37 · see citing works
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Tumor‑induced DNA methylation in the white blood cells of patients with colorectal cancer
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Self-citationLINE-1 and Alu hypomethylation in mucoepidermoid carcinoma
Sirivanichsuntorn, P., Keelawat, S., Danuthai, K., Mutirangura, A., Subbalekha, K., & Kitkumthorn, N. (2013) · BMC Clinical Pathology · doi:10.1186/1472-6890-13-10 · Cited by 32 · see citing works
Self-citationCircadian disruption and breast cancer: An epigenetic link?
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Alu Hypomethylation in Smoke-Exposed Epithelia and Oral Squamous Carcinoma
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Self-citationTRH site-specific methylation in oral and oropharyngeal squamous cell carcinoma
Puttipanyalears, C., Arayataweegool, A., Chalertpet, K., Rattanachayoto, P., Mahattanasakul, P., Tangjaturonsasme, N., Kerekhanjanarong, V., Mutirangura, A., & Kitkumthorn, N. (2018) · BMC Cancer · doi:10.1186/s12885-018-4706-x · Cited by 27 · see citing works
Self-citationMetformin: Sentinel of the Epigenetic Landscapes That Underlie Cell Fate and Identity
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Higher Alu Methylation Levels in Catch-Up Growth in Twenty-Year-Old Offsprings
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Epigenetic mechanisms in odontogenic tumors: A literature review
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Non-coding parts of genomes as the basis of epigenetic heredity
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Evaluation of NID2 promoter methylation for screening of Oral squamous cell carcinoma
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Detection of LINE-1 hypomethylation in cfDNA of Esophageal Adenocarcinoma Patients
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Human RNA-Directed DNA Methylation Methylates High-Mobility Group Box 1 Protein-Produced DNA Gaps
Watcharanurak, P., & Mutirangura, A. (2022) · Epigenomics · doi:10.2217/epi-2022-0022 · Cited by 21 · see citing works
Self-citationDNA methylation analysis of SOCS1, SOCS3, and LINE-1 in microdissected gingival tissue
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LINE-1 hypomethylation is not a common event in preneoplastic stages of gastric carcinogenesis
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Repetitive Element DNA Methylation is Associated with Menopausal Age
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Self-citationThe Role of Transposons in Epigenetic Regulation of Ontogenesis
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LINE-1 Methylation Patterns as a Predictor of Postmolar Gestational Trophoblastic Neoplasia
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Self-citationAnalysis of methylation microarray for tissue specific detection
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Self-citationAlu Methylation in Serum from Patients with Nasopharyngeal Carcinoma
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Altered immune phenotype and DNA methylation in panic disorder
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Roles of Intragenic and Intergenic L1s in Mouse and Human
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PDGFB hypomethylation is a favourable prognostic biomarker in primary myelofibrosis
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Self-citationAberrant methylation of the TERT promoter in esophageal squamous cell carcinoma
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DNA methylation in the genesis, progress and prognosis of head and neck cancer
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- Authors
- Kitkumthorn, N., & Mutirangura, A.
- Affiliations
- Mahidol University (TH)
- Chulalongkorn University (TH)
- Corresponding author
- Mutirangura, Apiwat
- Venue
- Clinical Epigenetics
- Published
- 2011-04-10
- Volume
- 2
- Issue
- 2
- Pages
- 315-330
- ISSN
- 1868-7075 (ISSN-L)
- 1868-7083
- PMC
- PMC3365388
- OpenAlex
- W2052350723
- Cited by
- 142
- References
- 137
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 7 · 2022: 9 · 2021: 7 · 2020: 7 · 2019: 11 · 2018: 15 · 2017: 17 · 2016: 6 · 2015: 15 · 2014: 14 · 2013: 15 · 2012: 8
- FWCI
- 5.07
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Clinical Epigenetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Chulalongkorn University
- Thailand Research Fund
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- LINE-1 hypomethylation, DNA methylation, cancer epigenetics, carcinogenesis, cancer screening, cancer risk assessment, tumor staging, prognostic factors, genomic instability, gene expression changes
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