Long Interspersed Element–1 (LINE-1): Passenger or Driver in Human Neoplasms?

LINE-1 (L1) retrotransposons make up a significant portion of human genomes, with an estimated 500,000 copies per genome. Like other retrotransposons, L1 retrotransposons propagate through RNA sequences that are reverse transcribed into DNA sequences, which are integrated into new genomic loci. L1 somatic insertions have the potential to disrupt the transcriptome by inserting into or nearby genes. By mutating genes and playing a role in epigenetic dysregulation, L1 transposons may contribute to tumorigenesis. Studies of the “mobilome” have lagged behind other tumor characterizations at the sequence, transcript, and epigenetic levels. Here, we consider evidence that L1 retrotransposons may sometimes drive human tumorigenesis.

• Publication year

  2013

• Venue

  PLoS Genetics

• Publication date

  2013-03-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1371/journal.pgen.1003402PMID 23555307PMCID 3610623
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Extensive somatic L1 retrotransposition in colorectal tumors

  2012cited by this paper
• Landscape of Somatic Retrotransposition in Human Cancers

  2012cited by this paper
• Somatic retrotransposition alters the genetic landscape of the human brain

  2011cited by this paper
• Repetitive Elements May Comprise Over Two-Thirds of the Human Genome

  2011cited by this paper
• Biological and clinical relevance of quantitative global methylation of repetitive DNA sequences in chronic lymphocytic leukemia

  2011cited by this paper
• Effect of reverse transcriptase inhibitors on LINE-1 and Ty1 reverse transcriptase activities and on LINE-1 retrotransposition

  2011cited by this paper
• Aberrant Overexpression of Satellite Repeats in Pancreatic and Other Epithelial Cancers

  2011cited by this paper
• Intrinsic restriction activity by apolipoprotein B mRNA editing enzyme APOBEC1 against the mobility of autonomous retrotransposons

  2011cited by this paper
• Natural mutagenesis of human genomes by endogenous retrotransposons.

  2010cited by this paper
• Somatic expression of LINE-1 elements in human tissues

  2010cited by this paper
• Association of nuclear localization of a long interspersed nuclear element-1 protein in breast tumors with poor prognostic outcomes.

  2010influential reference
• L1 retrotransposition in neurons is modulated by MeCP2

  2010cited by this paper
• All y'all need to know 'bout retroelements in cancer.

  2010cited by this paper
• Demethylation of a LINE-1 antisense promoter in the cMet locus impairs Met signalling through induction of illegitimate transcription

  2010cited by this paper
• Genome architecture marked by retrotransposons modulates predisposition to DNA methylation in cancer.

  2010cited by this paper
• Epigenetic silencing of engineered L1 retrotransposition events in human embryonic carcinoma cells

  2010cited by this paper
• Variable tandem repeats accelerate evolution of coding and regulatory sequences.

  2010cited by this paper
• The Reverse Transcription Inhibitor Abacavir Shows Anticancer Activity in Prostate Cancer Cell Lines

  2010cited by this paper
• Hypomethylation of a LINE-1 Promoter Activates an Alternate Transcript of the MET Oncogene in Bladders with Cancer

  2010cited by this paper
• Epigenetic control of mammalian LINE-1 retrotransposon by retinoblastoma proteins.

  2009cited by this paper
• Differential repetitive DNA methylation in multiple myeloma molecular subgroups.

  2009cited by this paper
• The regulated retrotransposon transcriptome of mammalian cells

  2009influential reference
• Nuclear receptor-induced chromosomal proximity and DNA breaks underlie specific translocations in cancer.

  2009cited by this paper
• Isolation of cancer-specific chimeric transcripts induced by hypomethylation of the LINE-1 antisense promoter.

  2009cited by this paper
• ERCC1/XPF limits L1 retrotransposition.

  2008cited by this paper
• Trex1 prevents cell-intrinsic initiation of autoimmunity.

  2008cited by this paper
• L1 mobile element expression causes multiple types of toxicity.

  2008cited by this paper
• DNA hypomethylation caused by Lsh deletion promotes erythroleukemia development

  2008cited by this paper
• Nucleoside Analogue Reverse Transcriptase Inhibitors Differentially Inhibit Human LINE-1 Retrotransposition

  2008cited by this paper
• Expression of LINE-1 p40 protein in pediatric malignant germ cell tumors and its association with clinicopathological parameters: a report from the Children's Oncology Group.

  2007influential reference
• MIWI2 is essential for spermatogenesis and repression of transposons in the mouse male germline.

  2007cited by this paper
• Cellular inhibitors of long interspersed element 1 and Alu retrotransposition.

  2006cited by this paper
• The human LINE-1 retrotransposon creates DNA double-strand breaks.

  2006cited by this paper
• Fitness cost of LINE-1 (L1) activity in humans.

  2006influential reference
• Multiple forms of genetic instability within a 2‐Mb chromosomal segment of 3q26.3–q27 are associated with development of esophageal adenocarcinoma

  2006cited by this paper
• Promoter hypomethylation of the LINE-1 retrotransposable elements activates sense/antisense transcription and marks the progression of chronic myeloid leukemia

  2005cited by this paper
• Inhibition of endogenous reverse transcriptase antagonizes human tumor growth

  2005cited by this paper
• Somatic mosaicism in neuronal precursor cells mediated by L1 retrotransposition

  2005cited by this paper
• Meiotic catastrophe and retrotransposon reactivation in male germ cells lacking Dnmt3L

  2004cited by this paper
• Lsh, an epigenetic guardian of repetitive elements.

  2004cited by this paper
• Growth retardation and premature aging phenotypes in mice with disruption of the SNF2-like gene, PASG.

  2004cited by this paper
• Exposure of normal and transformed cells to nevirapine, a reverse transcriptase inhibitor, reduces cell growth and promotes differentiation

  2003cited by this paper
• Human l1 retrotransposition is associated with genetic instability in vivo.

  2002cited by this paper
• Cooperativity between DNA Methyltransferases in the Maintenance Methylation of Repetitive Elements

  2002cited by this paper
• Disruption of the APC gene by a retrotransposal insertion of L1 sequence in a colon cancer.

  1992cited by this paper
• Insertional mutagenesis of the myc locus by a LINE-1 sequence in a human breast carcinoma

  1988cited by this paper
• SINEs and LINEs: highly repeated short and long interspersed sequences in mammalian genomes.

  1982cited by this paper

• A multi-analyte liquid biopsy approach for nonseminomatous testicular germ cell tumors: combining cfDNA and N-glycan analysis in blood and seminal plasma

  2025cites this paper
• Recent Non-LTR Retrotransposon Activity Predicts Cancer Prevalence in Mammals

  2025cites this paper
• Dysregulation of Locus-Specific Repetitive Elements in TCGA Pan-Cancers

  2025cites this paper
• SEQSIM: A novel bioinformatics tool for comparisons of promoter regions—a case study of calcium binding protein spermatid associated 1 (CABS1)

  2025cites this paper
• Role of EhLINE1_ORF1p outside retrotransposition: Downregulation causes growth defects in Entamoeba histolytica

  2025cites this paper
• BORIS/CTCFL epigenetically reprograms clustered CTCF binding sites into alternative transcriptional start sites

  2024cites this paper
• L1 pseudogenes of the erythrocyte blood fraction in patients with malignant tumors

  2024cites this paper
• A hypothesis about interrelations of epigenetic factors and transposable elements in memory formation

  2024cites this paper
• Molecular Complexity of Colorectal Cancer: Pathways, Biomarkers, and Therapeutic Strategies

  2024cites this paper
• SAM-DNMT3A, a strategy for induction of genome-wide DNA methylation, identifies DNA methylation as a vulnerability in ER-positive breast cancers

  2024cites this paper
• Anti-HERV-K Drugs and Vaccines, Possible Therapies against Tumors

  2023cites this paper
• Cancer Relevance of Circulating Antibodies Against LINE-1 Antigens in Humans

  2023cites this paper
• Interstrand crosslinking oligonucleotides elucidate the effect of metal ions on the methylation status of repetitive DNA elements

  2023cites this paper
• Ribonucleoprotein condensation driven by retrotransposon LINE-1 sustains RNA integrity and translation in mouse spermatocytes

  2023cites this paper
• Focusing on colorectal cancer in young adults (Review)

  2023cites this paper
• The Regulation and Immune Signature of Retrotransposons in Cancer

  2023cites this paper
• Hypomethylation of Long Interspersed Nucleotide Elements and Aldehyde Dehydrogenase in Patients of Alcohol Use Disorder with Cirrhosis

  2023cites this paper
• Retrotransposon LINE-1 bodies in the cytoplasm of piRNA-deficient mouse spermatocytes: Ribonucleoproteins overcoming the integrated stress response

  2023cites this paper
• Air Pollution and Human Endogenous Retrovirus Methylation in the School Inner-City Asthma Intervention Study.

  2023cites this paper
• Hyperarousal Symptom Severity in Women with Posttraumatic Stress Disorder Might Be Associated with LINE-1 Hypomethylation in Childhood Sexual Abuse Victims

  2023cites this paper
• Global DNA hypomethylation of colorectal tumours detected in tissue and liquid biopsies may be related to decreased methyl-donor content

  2022cites this paper
• Melatonin: Regulation of Viral Phase Separation and Epitranscriptomics in Post-Acute Sequelae of COVID-19

  2022cites this paper
• Association between toxic and essential metals in blood and global DNA methylation among electronic waste workers in Agbogbloshie, Ghana

  2022cites this paper
• NOS2 and S-nitrosothiol signaling induces DNA hypomethylation and LINE-1 retrotransposon expression

  2022cites this paper
• The insertion and dysregulation of transposable elements in osteosarcoma and their association with patient event-free survival

  2022cites this paper
• Methodological and Biological Factors Influencing Global DNA Methylation Results Measured by LINE-1 Pyrosequencing Assay in Colorectal Tissue and Liquid Biopsy Samples

  2022cites this paper
• Subclone Eradication Analysis Identifies Targets for Enhanced Cancer Therapy and Reveals L1 Retrotransposition as a Dynamic Source of Cancer Heterogeneity

  2021cites this paper
• ADAR1 RNA editing enzyme regulates R-loop formation and genome stability at telomeres in cancer cells

  2021cites this paper
• Changes in DNA methylation persist over time in males with severe alcohol use disorder—A longitudinal follow‐up study

  2021cites this paper
• Transposable element regulation and expression in cancer

  2021cites this paper
• Regulation of the epigenetic landscape by immune cell oxidants.

  2021cites this paper
• Phyllanthus debilis Methanolic Extract Reduces the Viability of Human Colorectal Adenocarcinoma (HT-29) Cells and Increases LINE-1 and Alu DNA Methylation

  2021cites this paper
• Computational modeling of RNase, antisense ORF0 RNA, and intracellular compartmentation and their impact on the life cycle of the line retrotransposon

  2021influential citation
• One-carbon metabolism and global DNA methylation in mothers of individuals with Down syndrome

  2021cites this paper
• Reverse transcriptase inhibition potentiates target therapy in BRAF-mutant melanomas: effects on cell proliferation, apoptosis, DNA-damage, ROS induction and mitochondrial membrane depolarization

  2020cites this paper
• Demethylated HSATII DNA And HSATII RNA Foci Sequester PRC1 Demethylated HSATII DNA And HSATII RNA Foci Sequester PRC1 And MeCP2 Into Cancer-Specific Nuclear Bodies And MeCP2 Into Cancer-Specific Nuclear Bodies

  2020cites this paper
• Expandable and reversible copy number amplification drives rapid adaptation to antifungal drugs

  2020cites this paper
• New Understanding of the Relevant Role of LINE-1 Retrotransposition in Human Disease and Immune Modulation

  2020cites this paper
• СИСТЕМНИЙ АНАЛІЗ АКТИВНОСТІ мікроРНК ПРИ ПУХЛИННОМУ ЗРОСТАННІ

  2020cites this paper
• Histone Methyltransferase SETDB1: A Common Denominator of Tumorigenesis with Therapeutic Potential

  2020cites this paper
• Efavirenz as a potential drug for the treatment of triple-negative breast cancers

  2020cites this paper
• Characterization of functional transposable element enhancers in acute myeloid leukemia

  2020influential citation
• Reverse transcriptase inhibitors promote the remodeling of nuclear architecture and induce autophagy in prostate cancer cells.

  2020cites this paper
• An overview about DNA methylation in childhood obesity: Characteristics of the studies and main findings

  2019cites this paper
• Oxidative stress and LINE-1 reactivation in bladder cancer are epigenetically linked through active chromatin formation.

  2019cites this paper
• Long interspersed nuclear element-1 mobilization as a target in cancer diagnostics, prognostics and therapeutics.

  2019cites this paper
• Soy Isoflavone Supplementation Increases Long Interspersed Nucleotide Element-1 (LINE-1) Methylation in Head and Neck Squamous Cell Carcinoma

  2019cites this paper
• Expression of L1 retrotransposon open reading frame protein 1 (L1ORF1p) in gynecologic cancers.

  2019cites this paper
• Mosaic APP Gene Recombination in Alzheimer’s Disease—What’s Next?

  2019cites this paper
• Transition from normal to cancerous cell by precancerous niche (PCN) induced chronic cell-matrix stress

  2019cites this paper
• Genome plasticity in Candida albicans is driven by long repeat sequences

  2019cites this paper
• The Relationship between Transposons and Transcription Factors in the Evolution of Eukaryotes

  2019cites this paper
• LINE-1 retrotransposition impacts the genome of human pre-implantation embryos and extraembryonic tissues

  2019cites this paper
• Characterization of SIRT1/DNMTs Functions and LINE-1 Methylation in Patients with Age-Related Macular Degeneration

  2019cites this paper
• Retroelement-Linked H3K4me1 Histone Tags Uncover Regulatory Evolution Trends of Gene Enhancers and Feature Quickly Evolving Molecular Processes in Human Physiology

  2019cites this paper
• Effects of the pesticide chlorpyrifos on breast cancer disease. Implication of epigenetic mechanisms.

  2019cites this paper
• Long interspersed nucleotide element-1 (LINE-1) methylation in colorectal cancer.

  2019cites this paper
• Chapter 2 Dietary Restriction , Dietary Design and the Epigenetics of Aging and Longevity

  2019cites this paper
• Progerin expression induces a significant downregulation of transcription from human repetitive sequences in iPSC-derived dopaminergic neurons

  2019cites this paper
• Prospects in the Search for Peptides for Specific Regulation of Aging

  2019cites this paper
• Epigenetic Biomarkers in Colorectal Cancer Patients Receiving Adjuvant or Neoadjuvant Therapy: A Systematic Review of Epidemiological Studies

  2019cites this paper
• Prostate-specific loss of UXT promotes cancer progression

  2019cites this paper
• SIRT7 mediates L1 elements transcriptional repression and their association with the nuclear lamina

  2019cites this paper
• Resveratrol Modulates SIRT1 and DNMT Functions and Restores LINE-1 Methylation Levels in ARPE-19 Cells under Oxidative Stress and Inflammation

  2018cites this paper
• Curcumin Modulates DNA Methyltransferase Functions in a Cellular Model of Diabetic Retinopathy

  2018cites this paper
• Line-1: Implications in the etiology of cancer, clinical applications, and pharmacologic targets.

  2018cites this paper
• APOBEC3B Activity Is Prevalent in Urothelial Carcinoma Cells and Only Slightly Affected by LINE-1 Expression

  2018cites this paper
• Linked read technology for assembling large complex and polyploid genomes

  2018cites this paper
• Passenger or Driver: Can Gene Expression Profiling Tell Us Anything about LINE-1 in Cancer?

  2018cites this paper
• AFLP-AFLP in silico-NGS approach reveals polymorphisms in repetitive elements in the malignant genome

  2018cites this paper
• Neonatal Bloodspot DNA Methylation Patterns are Associated with Childhood Weight Status in the Healthy Families Project

  2018cites this paper
• Colorectal Cancers: An Update on Their Molecular Pathology

  2018cites this paper
• The role of cell-free DNA in predicting colorectal cancer prognosis

  2018cites this paper
• LINE-1 ORF1 Protein Is Up-regulated by Reactive Oxygen Species and Associated with Bladder Urothelial Carcinoma Progression.

  2018cites this paper
• Mobile Genetic Elements in Cellular Differentiation, Genome Stability, and Cancer

  2018influential citation
• Interaction of Zinc Finger Proteins 146 & 507 with the Transposable Element LINE-1

  2018influential citation
• The Effect of Light Exposure at Night (LAN) on Carcinogenesis via Decreased Nocturnal Melatonin Synthesis

  2018cites this paper
• Resveratrol Restores LINE-1 Methylation Levels by Modulating SIRT1 and DNMTs Functions in Cellular Models of Age-Related Macular Degeneration

  2018cites this paper
• A study of meiomitosis and novel pathways of genomic instability in cutaneous T-cell lymphomas (CTCL)

  2018cites this paper
• ViFi: accurate detection of viral integration and mRNA fusion reveals indiscriminate and unregulated transcription in proximal genomic regions in cervical cancer

  2018cites this paper
• LINE-1 as a therapeutic target for castration-resistant prostate cancer.

  2018cites this paper
• Recently active transposable elements provide insights into the evolution of mammalian circular RNAs

  2017cites this paper
• Sodium bisulfite pyrosequencing revealed that developmental exposure to environmental contaminant mixtures does not affect DNA methylation of DNA repeats in Sprague-Dawley rats

  2017cites this paper
• Defective regulation of L1 endogenous retroelements in primary Sjogren's syndrome and systemic lupus erythematosus: Role of methylating enzymes.

  2017cites this paper
• Prognostic significance of LINE-1 hypomethylation in oropharyngeal squamous cell carcinoma

  2017cites this paper
• Methylation Levels of LINE-1 As a Useful Marker for Venous Invasion in Both FFPE and Frozen Tumor Tissues of Gastric Cancer

  2017cites this paper
• Demethylated HSATII DNA and HSATII RNA Foci Sequester PRC1 and MeCP2 into Cancer-Specific Nuclear Bodies.

  2017cites this paper
• Natural Selection in Cancer Biology: From Molecular Snowflakes to Trait Hallmarks.

  2017cites this paper
• Prediction of genome-wide DNA methylation in repetitive elements

  2017cites this paper
• Intact piRNA pathway prevents L1 mobilization in male meiosis

  2017cites this paper
• Tumoral LINE-1 hypomethylation is associated with poor survival of patients with intrahepatic cholangiocarcinoma

  2017cites this paper
• Global hypomethylation is an independent prognostic factor in diffuse large B cell lymphoma

  2017cites this paper
• LINE-1 methylation in peripheral blood leukocytes and clinical characteristics and prognosis of prostate cancer patients

  2017cites this paper
• Line1: Implications in the Etiology of Human Diseases, Clinical Utilities, and Pharmacological Target for Disease Treatment

  2017cites this paper
• In Vitro Transduction and Target-Mutagenesis Efficiency of HIV-1 pol Gene Targeting ZFN and CRISPR/Cas9 Delivered by Various Plasmids and/or Vectors: Toward an HIV Cure

  2017cites this paper
• Transposable element polymorphisms and human genome regulation

  2017cites this paper
• Prenatal dexamethasone exposure: glucocrticoid programming of the brain

  2016cites this paper
• Deciphering fact from artifact when using reporter assays to investigate the roles of host factors on L1 retrotransposition

  2016cites this paper
• Do the Human Endogenous Retroviruses Play a Role in Colon Cancer

  2016cites this paper
• Transposable elements: The enemies within.

  2016cites this paper