Evidence map›Paper›PMID 22797812›Full record

ArticleOncology reports2012

Association of epigenetic inactivation of the WRN gene with anticancer drug sensitivity in cervical cancer cells.

Kenta Masuda, Kouji Banno, Megumi Yanokura, Kosuke Tsuji, Yusuke Kobayashi, Iori Kisu, Arisa Ueki, Wataru Yamagami, Hiroyuki Nomura, Eiichiro Tominaga and 2 more

Open access · bronzeAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.3field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
  2. PLK1 phosphorylates WRN at replication forks.The Journal of pharmacology and experimental therapeutics · 2025
    Article
  3. Review
  4. Article
  5. Review
  6. RecQ Helicase Somatic Alterations in Cancer.Frontiers in molecular biosciences · 2022
    Review
  7. Article
  8. Review
  9. Article
  10. Article
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  12. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 1 institution in 1 country.

Kenta MasudaDepartment of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan.
Kouji Banno
Megumi Yanokura
Kosuke Tsuji
Yusuke Kobayashi
Iori Kisu
Arisa Ueki
Wataru Yamagami
Hiroyuki Nomura
Eiichiro Tominaga
Nobuyuki Susumu
Daisuke Aoki
Keio University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

DNA MethylationAdenocarcinomaAntineoplastic AgentsAzacitidineCamptothecinCarcinoma, Squamous CellCell Line, TumorDecitabineEpigenesis, GeneticExodeoxyribonucleasesFemaleGene Expression Regulation, NeoplasticHumansIrinotecanRecQ HelicasesRNA, Small InterferingAntineoplastic AgentsAzacitidineCamptothecinDecitabineExodeoxyribonucleasesIrinotecanRecQ HelicasesRNA, Small InterferingTopoisomerase I InhibitorsWerner Syndrome HelicaseWRN protein, human

Identifiers

PMID22797812
PMCPMC3583574
OpenAlexW2165666807

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.