Evidence map›Paper›PMID 23522960›Full record

ArticleMolecular oncology2013

Functional validation of putative tumor suppressor gene C13ORF18 in cervical cancer by Artificial Transcription Factors.

Christian Huisman, G Bea A Wisman, Hinke G Kazemier, Marcel A T M van Vugt, Ate G J van der Zee, Ed Schuuring, Marianne G Rots

Open access · bronzeAbstract read
In one paragraph

Article in Molecular oncology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

21 citing papers in PubMed, 42 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Article
  6. Limited Role of Promoter Methylation ofChinese medical journal · 2018
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  7. OncoTargets and therapy · 2018
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  12. Molecular events leading to HPV-induced high grade neoplasia.Papillomavirus research (Amsterdam, Netherlands) · 2016
    Review
  13. Article
  14. Article
  15. Review
  16. Article
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  18. Review
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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

7 authors at 1 institution in 1 country.

Christian HuismanDept. of Pathology and Medical Biology, University Medical Centre Groningen (UMCG), University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. c.huisman@umcg.nl
G Bea A Wisman
Hinke G Kazemier
Marcel A T M van Vugt
Ate G J van der Zee
Ed Schuuring
Marianne G Rots
University Medical Center Groningen · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

C13ORF18 is frequently hypermethylated in cervical cancer but not in normal cervix and might serve as a biomarker for the early detection of cervical cancer in scrapings. As hypermethylation is often observed for silenced tumor suppressor genes (TSGs), hypermethylated biomarker genes might exhibit tumor suppressive activities upon re-expression. Epigenetic drugs are successfully exploited to reverse TSG silencing, but act genome-wide. Artificial Transcription Factors (ATFs) provide a gene-specific approach for re-expression of silenced genes. Here, we investigated the potential tumor suppressive role of C13ORF18 in cervical cancer by ATF-induced re-expression. Five zinc finger proteins were engineered to bind the C13ORF18 promoter and fused to a strong transcriptional activator. C13ORF18 expression could be induced in cervical cell lines: ranging from >40-fold in positive (C13ORF18-unmethylated) cells to >110-fold in negative (C13ORF18-methylated) cells. Re-activation of C13ORF18 resulted in significant cell growth inhibition and/or induction of apoptosis. Co-treatment of cell lines with ATFs and epigenetic drugs further enhanced the ATF-induced effects. Interestingly, re-activation of C13ORF18 led to partial demethylation of the C13ORF18 promoter and decreased repressive histone methylation. These data demonstrate the potency of ATFs to re-express and potentially demethylate hypermethylated silenced genes. Concluding, we show that C13ORF18 has a TSG function in cervical cancer and may serve as a therapeutic anti-cancer target. As the amount of epimutations in cancer exceeds the number of gene mutations, ATFs provide promising tools to validate hypermethylated marker genes as therapeutic targets.

Indexed as

Genes, Tumor SuppressorCell Line, TumorCervix UteriDNA MethylationFemaleGene Expression Regulation, NeoplasticHumansPromoter Regions, GeneticTranscription FactorsTumor Suppressor ProteinsUterine Cervical NeoplasmsRUBCNL protein, humanTranscription FactorsTumor Suppressor Proteins

Identifiers

PMID23522960
PMCPMC5528488
OpenAlexW2108090479

What OpenQuestion holds

Textmetadata
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.