ArticleEpigenetics2015
Longitudinal assessment of DNA methylation changes during HPVE6E7-induced immortalization of primary keratinocytes.
Article in Epigenetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- FAM19A4 and miR124-2 methylation status in human papillomavirus-driven and human papillomavirus-negative oropharyngeal squamous cell carcinomas.Infectious agents and cancer · 2025Article
- Repression of CADM1 transcription by HPV type 18 is mediated by three-dimensional rearrangement of promoter-enhancer interactions.PLoS pathogens · 2025Article
- Loss of keratin 14 expression from immortalized keratinocytes by promoter methylation.Experimental dermatology · 2024Article
- The Drivers, Mechanisms, and Consequences of Genome Instability in HPV-Driven Cancers.Cancers · 2022Review
- ERBB3 methylation and immune infiltration in tumor microenvironment of cervical cancer.Scientific reports · 2022Article
- The use of host cell DNA methylation analysis in the detection and management of women with advanced cervical intraepithelial neoplasia: a review.BJOG : an international journal of obstetrics and gynaecology · 2021Review
- DNA methylation markers as a triage test for identification of cervical lesions in a high risk human papillomavirus positive screening cohort.International journal of cancer · 2019Article
- HPV16-Related Cervical Cancers and Precancers Have Increased Levels of Host Cell DNA Methylation in Women Living with HIV.International journal of molecular sciences · 2018Article
- Telomeres and Telomerase During Human Papillomavirus-Induced Carcinogenesis.Molecular diagnosis & therapy · 2018Review
- DNA Tumor Virus Regulation of Host DNA Methylation and Its Implications for Immune Evasion and Oncogenesis.Viruses · 2018Review
- Telomerase activity in cervical scrapes of women with high-grade cervical disease: A nested case-control study.Oncology letters · 2018Article
- Methylomics of nitroxidative stress on precancerous cells reveals DNA methylation alteration at the transition fromOncotarget · 2017Article
- Telomerase Induction in HPV Infection and Oncogenesis.Viruses · 2017Review
- High-Risk Human Papillomavirus E7 Alters Host DNA Methylome and Represses HLA-E Expression in Human Keratinocytes.Scientific reports · 2017Article
- Epigenetic and genetic dissections of UV-induced global gene dysregulation in skin cells through multi-omics analyses.Scientific reports · 2017Article
- HPV8-E6 Interferes with Syntenin-2 Expression through Deregulation of Differentiation, Methylation and Phosphatidylinositide-Kinase Dependent Mechanisms.Frontiers in microbiology · 2017Article
- Molecular events leading to HPV-induced high grade neoplasia.Papillomavirus research (Amsterdam, Netherlands) · 2016Review
- Immortalization capacity of HPV types is inversely related to chromosomal instability.Oncotarget · 2016Article
- Model systems to study the life cycle of human papillomaviruses and HPV-associated cancers.Virologica Sinica · 2015Review
- Aberrant Hypermethylation of SALL3 with HPV Involvement Contributes to the Carcinogenesis of Cervical Cancer.PloS one · 2015Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High-risk human papillomavirus (hrHPV)-induced immortalization and malignant transformation are accompanied by DNA methylation of host genes. To determine when methylation is established during cell immortalization and whether it is hrHPV-type dependent, DNA methylation was studied in a large panel of HPVE6E7-immortalized keratinocyte cell lines. These cell lines displayed different growth behaviors, i.e., continuous growth versus crisis period prior to immortalization, reflecting differential immortalization capacities of the 7 HPV-types (16/18/31/33/45/66/70) studied. In this study, cells were monitored for hypermethylation of 14 host genes (APC, CADM1, CYGB, FAM19A4, hTERT, mir124-1, mir124-2, mir124-3, MAL, PHACTR3, PRDM14, RASSF1A, ROBO3, and SFRP2) at 4 different stages during immortalization. A significant increase in overall methylation levels was seen with progression through each stage of immortalization. At stage 1 (pre-immortalization), a significant increase in methylation of hTERT, mir124-2, and PRDM14 was already apparent, which continued over time. Methylation of ROBO3 was significantly increased at stage 2 (early immortal), followed by CYGB (stage 3) and FAM19A4, MAL, PHACTR3, and SFRP2 (stage 4). Methylation patterns were mostly growth behavior independent. Yet, hTERT methylation levels were significantly increased in cells that just escaped from crisis. Bisulfite sequencing of hTERT confirmed increased methylation in immortal cells compared to controls, with the transcription core and known repressor sites remaining largely unmethylated. In conclusion, HPV-induced immortalization is associated with a sequential and progressive increase in promoter methylation of a subset of genes, which is mostly independent of the viral immortalization capacity.
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