ArticleOncology reports2012
Association of epigenetic inactivation of the WRN gene with anticancer drug sensitivity in cervical cancer cells.
Article in Oncology reports, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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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
17 citing papers in PubMed, 34 citations in OpenAlex.
- Pan-Cancer Analysis of WRN: From Multi-Omics Biomarker Discovery to Therapy-Guiding Functional Evidence.OncoTargets and therapy · 2026Article
- PLK1 phosphorylates WRN at replication forks.The Journal of pharmacology and experimental therapeutics · 2025Article
- Long noncoding RNAs involved in therapeutic response: implications for cervical cancer drug resistance.Frontiers in oncology · 2025Review
- A case of Bloom syndrome manifesting with therapy-related myelodysplastic syndromes harboring a novel BLM gene variant.International journal of hematology · 2024Article
- Epigenetic modulations in cancer: predictive biomarkers and potential targets for overcoming the resistance to topoisomerase I inhibitors.Annals of medicine · 2023Review
- RecQ Helicase Somatic Alterations in Cancer.Frontiers in molecular biosciences · 2022Review
- WRN inhibits oxidative stress-induced apoptosis of human lensepithelial cells through ATM/p53 signaling pathway and its expression is downregulated by DNA methylation.Molecular medicine (Cambridge, Mass.) · 2020Article
- Role of DNA Methylation in the Resistance to Therapy in Solid Tumors.Frontiers in oncology · 2020Review
- Association of CHFR Promoter Methylation with Treatment Outcomes of Irinotecan-Based Chemotherapy in Metastatic Colorectal Cancer.Neoplasia (New York, N.Y.) · 2019Article
- KLF5 promotes cervical cancer proliferation, migration and invasion in a manner partly dependent on TNFRSF11a expression.Scientific reports · 2017Article
- Epigenetic inactivation of tumour suppressor coding and non-coding genes in human cancer: an update.Open biology · 2017Review
- WRN Promoter CpG Island Hypermethylation Does Not Predict More Favorable Outcomes for Patients with Metastatic Colorectal Cancer Treated with Irinotecan-Based Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Article
- Epigenetic Regulation of Werner Syndrome Gene in Age-Related Cataract.Journal of ophthalmology · 2015Article
- Candidate biomarkers for cervical cancer treatment: Potential for clinical practice (Review).Molecular and clinical oncology · 2014Article
- Emerging biological treatments for uterine cervical carcinoma.Journal of Cancer · 2014Review
- Promoter hypermethylation of KLF4 inactivates its tumor suppressor function in cervical carcinogenesis.PloS one · 2014Article
- Discovering new medicines targeting helicases: challenges and recent progress.Journal of biomolecular screening · 2013Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Werner (WRN) gene codes for a DNA helicase that contributes to genomic stability and has been identified as the gene responsible for progeria. Recent studies have shown reduced WRN expression due to aberrant DNA hypermethylation in cancer cells. Furthermore, WRN expression is thought to affect sensitivity to DNA topoisomerase I inhibitors in cancer therapy. In this study, we examined the relationship between aberrant DNA hypermethylation of WRN and the sensitivity of cervical cancer cells to anticancer drugs. DNA was extracted from samples from 22 patients with primary cervical cancer and 6 human cervical cancer-derived cell lines. Aberrant DNA hypermethylation was analyzed by methylation-specific PCR. WRN expression in cultured cells before and after addition of 5-aza-2-deoxycytidine, a demethylating agent, was examined using RT-PCR. The sensitivity of cells to anticancer drugs was determined using a collagen gel droplet embedded culture drug sensitivity test (CD-DST). siRNA against WRN was transfected into a cervical cancer-derived cell line with high WRN expression. Changes in drug sensitivity after silencing WRN were determined by CD-DST. Aberrant DNA hypermethylation and decreased expression of WRN were detected in 7/21 cases of primary cervical cancer and in two cervical cancer-derived cell lines. These two cell lines showed high sensitivity to CPT-11, a topoisomerase I inhibitor, but became resistant to CPT-11 after treatment with 5-aza-2-deoxycytidine. Transfection of siRNA against WRN increased the sensitivity of the cells to CPT-11. Aberrant DNA hypermethylation of WRN also increased the sensitivity of cervical cancer cells to CPT-11. Therefore, epigenetic inactivation of this gene may be a biomarker for selection of drugs for the treatment of cervical cancer. This is the first report to show a relationship between the methylation of the WRN gene and sensitivity to CPT-11 in gynecological cancers.
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