Evidence map›Paper›PMID 25760330›Full record

ArticlePLoS pathogens2015

Dependence of intracellular and exosomal microRNAs on viral E6/E7 oncogene expression in HPV-positive tumor cells.

Anja Honegger, Daniela Schilling, Sandra Bastian, Jasmin Sponagel, Vladimir Kuryshev, Holger Sültmann, Martin Scheffner, Karin Hoppe-Seyler, Felix Hoppe-Seyler

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 159 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
159citing papers in PubMed, 1 pooled it
9.1field-weighted citation impact, top 1% 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

159 citing papers in PubMed, 1 synthesis or guideline pooled it, 244 citations in OpenAlex.

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99 more citing papers are in PubMed but not listed here.

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 4 institutions in 1 country.

Anja HoneggerMolecular Therapy of Virus-Associated Cancers (F065), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Daniela SchillingCancer Genome Research (B063), German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.
Sandra BastianMolecular Therapy of Virus-Associated Cancers (F065), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Jasmin SponagelMolecular Therapy of Virus-Associated Cancers (F065), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Vladimir KuryshevCancer Genome Research (B063), German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.
Holger SültmannCancer Genome Research (B063), German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.
Martin ScheffnerDepartment of Biology, University of Konstanz, Konstanz, Germany.
Karin Hoppe-SeylerMolecular Therapy of Virus-Associated Cancers (F065), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Felix Hoppe-SeylerMolecular Therapy of Virus-Associated Cancers (F065), German Cancer Research Center (DKFZ), Heidelberg, Germany.
German Cancer Research Center · DEDeutschen Konsortium für Translationale Krebsforschung · DEHeidelberg University · DEUniversity of Konstanz · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Specific types of human papillomaviruses (HPVs) cause cervical cancer. Cervical cancers exhibit aberrant cellular microRNA (miRNA) expression patterns. By genome-wide analyses, we investigate whether the intracellular and exosomal miRNA compositions of HPV-positive cancer cells are dependent on endogenous E6/E7 oncogene expression. Deep sequencing studies combined with qRT-PCR analyses show that E6/E7 silencing significantly affects ten of the 52 most abundant intracellular miRNAs in HPV18-positive HeLa cells, downregulating miR-17-5p, miR-186-5p, miR-378a-3p, miR-378f, miR-629-5p and miR-7-5p, and upregulating miR-143-3p, miR-23a-3p, miR-23b-3p and miR-27b-3p. The effects of E6/E7 silencing on miRNA levels are mainly not dependent on p53 and similarly observed in HPV16-positive SiHa cells. The E6/E7-regulated miRNAs are enriched for species involved in the control of cell proliferation, senescence and apoptosis, suggesting that they contribute to the growth of HPV-positive cancer cells. Consistently, we show that sustained E6/E7 expression is required to maintain the intracellular levels of members of the miR-17~92 cluster, which reduce expression of the anti-proliferative p21 gene in HPV-positive cancer cells. In exosomes secreted by HeLa cells, a distinct seven-miRNA-signature was identified among the most abundant miRNAs, with significant downregulation of let-7d-5p, miR-20a-5p, miR-378a-3p, miR-423-3p, miR-7-5p, miR-92a-3p and upregulation of miR-21-5p, upon E6/E7 silencing. Several of the E6/E7-dependent exosomal miRNAs have also been linked to the control of cell proliferation and apoptosis. This study represents the first global analysis of intracellular and exosomal miRNAs and shows that viral oncogene expression affects the abundance of multiple miRNAs likely contributing to the E6/E7-dependent growth of HPV-positive cancer cells.

Indexed as

ApoptosisCell Line, TumorCell ProliferationCellular SenescenceDNA-Binding ProteinsExosomesFemaleGenome-Wide Association StudyHigh-Throughput Nucleotide SequencingHumansImmunoblottingMicroRNAsMicroscopy, Electron, TransmissionOncogene Proteins, ViralPapillomavirus InfectionsRepressor ProteinsDNA-Binding ProteinsE6 protein, Human papillomavirus type 16E6 protein, Human papillomavirus type 18MicroRNAsOncogene Proteins, ViralRepressor Proteins

Identifiers

PMID25760330
PMCPMC4356518
OpenAlexW2087625283

What OpenQuestion holds

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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.