Evidence map›Paper›PMID 24460791›Full record

ArticleVirology journal2014

EBNA1 binding and epigenetic regulation of gastrokine tumor suppressor genes in gastric carcinoma cells.

Fang Lu, Italo Tempera, Hyunna T Lee, Karen Dewispelaere, Paul M Lieberman

Open access · goldAbstract read
In one paragraph

Article in Virology journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing 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

16 citing papers in PubMed, 23 citations in OpenAlex.

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  8. Research advances in the molecular classification of gastric cancer.Cellular oncology (Dordrecht, Netherlands) · 2024
    Review
  9. EBNA1 inhibitors have potent and selective antitumor activity in xenograft models of Epstein-Barr virus-associated gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2021
    Article
  10. 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

5 authors at 2 institutions in 1 country.

Fang Lu
Italo Tempera
Hyunna T Lee
Karen Dewispelaere
Paul M LiebermanThe Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA. Lieberman@wistar.org.
The Wistar Institute · USTemple University · US

Funding

Tumor Microenvironment and MetastasisP30CA010815 · NCI · WISTAR INSTITUTE · PI Alessandro Gardini · 1985 to 2026
$75.9M
Regulation of Epstein-Barr Virus LatencyR01CA093606 · NCI · WISTAR INSTITUTE · PI LIEBERMAN, PAUL M. · 2002 to 2022
$6.7M
Epigenetic Regulation of Epstein-Barr Virus Latency ProgramsR01DE017336 · NIDCR · WISTAR INSTITUTE · PI PAUL M. LIEBERMAN · 2005 to 2026
$6.5M
Regulation of EBV reactivationR01CA085678 · NCI · WISTAR INSTITUTE · PI LIEBERMAN, PAUL M. · 2001 to 2011
$2.7M
Regulation of EBV Latency by Chromosome ConformationK99AI099153 · NIAID · WISTAR INSTITUTE · PI TEMPERA, ITALO · 2012 to 2012
$109k
NCI NIH HHS CA085678NCI NIH HHS CA093606NCI NIH HHS P30 CA010815NCI NIH HHS P30 CA10815NCI NIH HHS R01 CA085678NCI NIH HHS R01 CA093606NIAID NIH HHS K99 AI099153NIDCR NIH HHS DE017336NIDCR NIH HHS R01 DE017336
6 · The paper itself

Abstract

backgroundEpstein-Barr Virus (EBV) latently infects ~10% of gastric carcinomas (GC). Epstein-Barr Nuclear Antigen 1 (EBNA1) is expressed in EBV-associated GC, and can bind host DNA, where it may impact cellular gene regulation. Here, we show that EBNA1 binds directly to DNA upstream of the divergently transcribed GC-specific tumor suppressor genes gastrokine 1 (GKN1) and gastrokine 2 (GKN2).

methodsWe use ChIP-Seq, ChIP-qPCR, and EMSA to demonstrate that EBNA1 binds directly to the GKN1 and GKN2 promoter locus. We generate AGS-EBV, and AGS-EBNA1 cell lines to study the effects of EBNA1 on GKN1 and GKN2 mRNA expression with or without 5' azacytidine treatment.

resultsWe show that gastrokine genes are transcriptionally silenced by DNA methylation. We also show that latent EBV infection further reduces GKN1 and GKN2 expression in AGS gastric carcinoma cells, and that siRNA depletion of EBNA1 partially alleviates this repression. However, ectopic expression of EBNA1 slightly increased GKN1 and GKN2 basal mRNA levels, but reduced their responsiveness to demethylating agent.

conclusionsThese findings demonstrate that EBNA1 binds to the divergent promoter of the GKN1 and GKN2 genes in GC cells, and suggest that EBNA1 contributes to the complex transcriptional and epigenetic deregulation of the GKN1 and GKN2 tumor suppressor genes in EBV positive GC.

Indexed as

Epigenesis, GeneticCarrier ProteinsCell Line, TumorEpstein-Barr Virus Nuclear AntigensHumansPeptide HormonesPromoter Regions, GeneticProtein BindingTumor Suppressor ProteinsCarrier ProteinsEBV-encoded nuclear antigen 1Epstein-Barr Virus Nuclear AntigensGKN1 protein, humanGKN2 protein, humanPeptide HormonesTumor Suppressor Proteins

Identifiers

PMID24460791
PMCPMC3904692
OpenAlexW2056127778

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.