Evidence map›Paper›PMID 32938703›Full record

ArticlemSphere2020

Werner Syndrome Protein (WRN) Regulates Cell Proliferation and the Human Papillomavirus 16 Life Cycle during Epithelial Differentiation.

Claire D James, Dipon Das, Ethan L Morgan, Raymonde Otoa, Andrew Macdonald, Iain M Morgan

Open access · goldAbstract read
In one paragraph

Article in mSphere, 2020. 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
1.1field-weighted citation impact, top 23% 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, 21 citations in OpenAlex.

  1. Article
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  10. Article
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  12. CRISPR-Cas9‒Based Genomic Engineering in Keratinocytes: From Technology to Application.JID innovations : skin science from molecules to population health · 2022
    Review
  13. RecQ Helicase Somatic Alterations in Cancer.Frontiers in molecular biosciences · 2022
    Review
  14. Review
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  16. 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

6 authors at 2 institutions in 2 countries.

Claire D JamesVirginia Commonwealth University (VCU), Philips Institute for Oral Health Research, School of Dentistry, Richmond, Virginia, USA.
Dipon DasVirginia Commonwealth University (VCU), Philips Institute for Oral Health Research, School of Dentistry, Richmond, Virginia, USA.
Ethan L MorganSchool of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, UK.ORCID 0000-0002-6487-5450
Raymonde OtoaVirginia Commonwealth University (VCU), Philips Institute for Oral Health Research, School of Dentistry, Richmond, Virginia, USA.
Andrew MacdonaldSchool of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, UK.ORCID 0000-0002-5978-4693
Iain M MorganVirginia Commonwealth University (VCU), Philips Institute for Oral Health Research, School of Dentistry, Richmond, Virginia, USA immorgan@vcu.edu.ORCID 0000-0002-4949-3032
Virginia Commonwealth University · USUniversity of Leeds · GB

Funding

Virus Vector Shared ResourceP30CA016059 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI Kim Felder Rhoads · 1985 to 2026
$51.0M
Medical Research Council MR/K012665Medical Research Council MR/S001697/1NCI NIH HHS P30 CA016059Wellcome TrustWellcome Trust 204825/Z/16/Z
6 · The paper itself

Abstract

Human papillomaviruses recruit a host of DNA damage response factors to their viral genome to facilitate homologous recombination replication in association with the viral replication factors E1 and E2. We previously demonstrated that SIRT1 deacetylation of WRN promotes recruitment of WRN to E1-E2 replicating DNA and that WRN regulates both the levels and fidelity of E1-E2 replication. The deacetylation of WRN by SIRT1 results in an active protein able to complex with replicating DNA, but a protein that is less stable. Here, we demonstrate an inverse correlation between SIRT1 and WRN in CIN cervical lesions compared to normal control tissue, supporting our model of SIRT1 deacetylation destabilizing WRN protein. We CRISPR/Cas9 edited N/Tert-1 and N/Tert-1+HPV16 cells to knock out WRN protein expression and subjected the cells to organotypic raft cultures. In N/Tert-1 cells without WRN expression, there was enhanced basal cell proliferation, DNA damage, and thickening of the differentiated epithelium. In N/Tert-1+HPV16 cells, there was enhanced basal cell proliferation, increased DNA damage throughout the epithelium, and increased viral DNA replication. Overall, the results demonstrate that the expression of WRN is required to control the proliferation of N/Tert-1 cells and controls the HPV16 life cycle in these cells. This complements our previous data demonstrating that WRN controls the levels and fidelity of HPV16 E1-E2 DNA replication. The results describe a new role for WRN, a tumor suppressor, in controlling keratinocyte differentiation and the HPV16 life cycle.

Indexed as

Cell DifferentiationCell Line, TransformedCell ProliferationCervix UteriDNA ReplicationDNA, ViralEpithelial CellsFemaleGene EditingGenome, ViralHost-Pathogen InteractionsHuman papillomavirus 16HumansKeratinocytesPapillomavirus InfectionsVirus ReplicationDNA, ViralWerner Syndrome HelicaseWRN protein, humancervical cancerDNA damageepithelial differentiationhead and neck cancerhuman papillomavirushuman papillomavirus 16keratinocytelife cyclereplicationSIRT1WernerWerner helicaseWRN

Identifiers

PMID32938703
PMCPMC7494838
OpenAlexW3087129465

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.