Evidence map›Paper›PMID 28881717›Full record

ArticleOncotarget2017

5-aza-2'-deoxycytidine (DAC) treatment downregulates the HPV E6 and E7 oncogene expression and blocks neoplastic growth of HPV-associated cancer cells.

Maximilian Stich, Lennard Ganss, Jens Puschhof, Elena-Sophie Prigge, Miriam Reuschenbach, Ana Guiterrez, Svetlana Vinokurova, Magnus von Knebel Doeberitz

Abstract read
In one paragraph

Article in Oncotarget, 2017. 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
–field-weighted citation impact
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.

  1. Review
  2. Review
  3. Effects of CpG sites methylation modification of HPV16 integration essential gene on the proliferation of cervical cancer cells.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023
    Article
  4. Review
  5. Article
  6. Observational
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Role of DNA methylation in HPV associated lesions.Papillomavirus research (Amsterdam, Netherlands) · 2019
    Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
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

8 authors.

Maximilian Stich *Department of Applied Tumor Biology, Institute of Pathology, University of Heidelberg, Germany.
Lennard Ganss *Department of Applied Tumor Biology, Institute of Pathology, University of Heidelberg, Germany.
Jens PuschhofDepartment of Applied Tumor Biology, Institute of Pathology, University of Heidelberg, Germany.
Elena-Sophie PriggeDepartment of Applied Tumor Biology, Institute of Pathology, University of Heidelberg, Germany.
Miriam ReuschenbachDepartment of Applied Tumor Biology, Institute of Pathology, University of Heidelberg, Germany.
Ana GuiterrezDepartment of Applied Tumor Biology, Institute of Pathology, University of Heidelberg, Germany.
Svetlana VinokurovaInstitute of Carcinogenesis, NN Blokhin Cancer Research Center, Moscow, Russia.
Magnus von Knebel DoeberitzDepartment of Applied Tumor Biology, Institute of Pathology, University of Heidelberg, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

High-risk human papillomaviruses (hr HPVs) may cause various human cancers and associated premalignant lesions. Transformation of the host cells is triggered by overexpression of the viral oncogenes E6 and E7 that deregulate the cell cycle and induce chromosomal instability. This process is accompanied by hypermethylation of distinct CpG sites resulting in silencing of tumor suppressor genes, inhibition of the viral E2 mediated control of E6 and E7 transcription as well as deregulated expression of host cell microRNAs. Therefore, we hypothesized that treatment with demethylating agents might restore those regulatory mechanisms. Here we show that treatment with 5-aza-2'-deoxycytidine (DAC) strongly decreases the expression of E6 and E7 in a panel of HPV-transformed cervical cancer and head and neck squamous cell carcinoma cell lines. Reduction of E6 and E7 further resulted in increased target protein levels including p53 and p21 reducing the proliferation rates and colony formation abilities of the treated cell lines. Moreover, DAC treatment led to enhanced expression of tumor the suppressive miRNA-375 that targets and degrades E6 and E7 transcripts. Therefore, we suggest that DAC treatment of HPV-associated cancers and respective precursor lesions may constitute a targeted approach to subvert HPV oncogene functions that deserves testing in clinical trials.

Indexed as

5-aza-2′-deoxycytidine (DAC)DNA demethylationHPVmiR-375upstream regulatory region (URR)

Identifiers

PMID28881717
PMCPMC5581016

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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.