Evidence mapPaperPMID 37565725Full record

ArticleJournal of medical virology2023

CREB1 activation promotes human papillomavirus oncogene expression and cervical cancer cell transformation.

Yigen Li, Molly R Patterson, Ethan L Morgan, Christopher W Wasson, Emma L Ryder, Diego Barba-Moreno, James A Scarth, Miao Wang, Andrew Macdonald

Open access · hybridAbstract read
In one paragraph

Article in Journal of medical virology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
3.2field-weighted citation impact, top 7% 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

12 citing papers in PubMed, 15 citations in OpenAlex.

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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

9 authors at 2 institutions in 1 country.

Yigen LiSchool of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, West Yorkshire, UK.ORCID 0000-0002-0420-214X
Molly R PattersonSchool of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, West Yorkshire, UK.
Ethan L MorganSchool of Life Sciences, University of Sussex, Falmer, Brighton, UK.ORCID 0000-0002-6487-5450
Christopher W WassonLeeds Institute of Rheumatic and Musculoskeletal Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, West Yorkshire, UK.
Emma L RyderSchool of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, West Yorkshire, UK.
Diego Barba-MorenoSchool of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, West Yorkshire, UK.
James A ScarthSchool of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, West Yorkshire, UK.
Miao WangSchool of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, West Yorkshire, UK.
Andrew MacdonaldSchool of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, West Yorkshire, UK.ORCID 0000-0002-5978-4693
University of Leeds · GBUniversity of Sussex · GB

Funding

Biotechnology and Biological Sciences Research Council BB/M011151/1Medical Research Council MR/K012665Medical Research Council MR/S001697/1Wellcome TrustWellcome Trust 204825/Z/16/Z
6 · The paper itself

Abstract

Human papillomaviruses (HPVs) infect the oral and anogenital mucosa and can cause cancer. The high-risk (HR)-HPV oncoproteins, E6 and E7, hijack cellular factors to promote cell proliferation, delay differentiation and induce genomic instability, thus predisposing infected cells to malignant transformation. cAMP response element (CRE)-binding protein 1 (CREB1) is a master transcription factor that can function as a proto-oncogene, the abnormal activity of which is associated with multiple cancers. However, little is known about the interplay between HPV and CREB1 activity in cervical cancer or the productive HPV lifecycle. We show that CREB is activated in productively infected primary keratinocytes and that CREB1 expression and phosphorylation is associated with the progression of HPV+ cervical disease. The depletion of CREB1 or inhibition of CREB1 activity results in decreased cell proliferation and reduced expression of markers of epithelial to mesenchymal transition, coupled with reduced migration in HPV+ cervical cancer cell lines. CREB1 expression is negatively regulated by the tumor suppressor microRNA, miR-203a, and CREB1 phosphorylation is controlled through the MAPK/MSK pathway. Crucially, CREB1 directly binds the viral promoter to upregulate transcription of the E6/E7 oncogenes, establishing a positive feedback loop between the HPV oncoproteins and CREB1. Our findings demonstrate the oncogenic function of CREB1 in HPV+ cervical cancer and its relationship with the HPV oncogenes.

Indexed as

Oncogene Proteins, ViralPapillomavirus InfectionsUterine Cervical NeoplasmsCyclic AMP Response Element-Binding ProteinEpithelial-Mesenchymal TransitionFemaleHuman Papillomavirus VirusesHumansOncogenesPapillomavirus E7 ProteinsRepressor ProteinsCREB1 protein, humanCyclic AMP Response Element-Binding ProteinOncogene Proteins, ViralPapillomavirus E7 ProteinsRepressor Proteinscervical cancerCREB1E6E7HPVmiR-203a

Identifiers

PMID37565725
PMCPMC10952218
OpenAlexW4385752119

What Socratic 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 Socratic graph.