Evidence map›Paper›PMID 23051921›Full record

ArticleEpigenetics2012

PGE2 induces interleukin-8 derepression in human astrocytoma through coordinated DNA demethylation and histone hyperacetylation.

Isabella Venza, Maria Visalli, Cinzia Fortunato, Manuela Ruggeri, Simona Ratone, Maria Caffo, Gerardo Caruso, Concetta Alafaci, Francesco Tomasello, Diana Teti and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Epigenetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 10% 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

24 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Chronic Exposure to Cadmium Induces Differential Methylation in Mice Spermatozoa.Toxicological sciences : an official journal of the Society of Toxicology · 2021
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  5. Immune response in glioma's microenvironment.Innovative surgical sciences · 2020
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  11. Review
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  15. Review
  16. MiRNA expression profiling in human gliomas: upregulated miR-363 increases cell survival and proliferation.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016
    Article
  17. Review
  18. Cellular Mechanisms of Oxidative Stress and Action in Melanoma.Oxidative medicine and cellular longevity · 2015
    Review
  19. Article
  20. Article
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

11 authors at 1 institution in 1 country.

Isabella VenzaDepartment of Surgical Specialities, University of Messina, Messina, Italy.
Maria Visalli
Cinzia Fortunato
Manuela Ruggeri
Simona Ratone
Maria Caffo
Gerardo Caruso
Concetta Alafaci
Francesco Tomasello
Diana Teti
Mario Venza
University of Messina · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We have recently reported that in astrocytoma cells the expression of interleukin-8 (IL-8) is upregulated by prostaglandin E2 (PGE2). Unfortunately, the exact mechanism by which this happens has not been clarified yet. Here, we have investigated whether IL-8 activation by PGE2 involves changes in DNA methylation and/or histone modifications in 46 astrocytoma specimens, two astrocytoma cell lines and normal astrocytic cells. The DNA methylation status of the IL-8 promoter was analyzed by bisulphite sequencing and by methylation DNA immunoprecipitation analysis. The involvement of DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), as well as histone acetylation levels, was assayed by chromatin immunoprecipitation. IL-8 expression at promoter, mRNA and protein level was explored by transfection, real-time PCR and enzyme immunoassay experiments in cells untreated or treated with PGE2, 5-aza-2'-deoxycytidine (5-aza-dC) and HDAC inhibitors, alone or in combination. EMSA was performed with crude cell extracts or recombinant protein. We observed that PGE2 induced IL-8 activation through: (1) demethylation of the single CpG site 5 located at position -83 within the binding region for CEBP-β in the IL-8 promoter; (2) C/EBP-β and p300 co-activator recruitment; (3) H3 acetylation enhancement and (4) reduction in DNMT1, DNMT3a, HDAC2 and HDAC3 association to CpG site 5 region. Treatment with 5-aza-dC or HDAC inhibitors of class I HDACs strengthened either basal or PGE2-mediated IL-8 expression. These findings have elucidated an orchestrated mechanism triggered by PGE2 whereby concurrent association of site-specific demethylation and histone H3 hyperacetylation resulted in derepression of IL-8 gene expression in human astrocytoma.

Indexed as

DNA MethylationGene Expression Regulation, NeoplasticProtein Processing, Post-TranslationalAcetylationAdolescentAdultBase SequenceBrain NeoplasmsCell Line, TumorCpG IslandsDinoprostoneDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADNA, NeoplasmFemaleDinoprostoneDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADNA, NeoplasmDNMT1 protein, humanDNMT3A protein, humanHDAC2 protein, humanHistone Deacetylase 2Histone Deacetylase 3Histone Deacetylase InhibitorsHistone DeacetylasesHistonesInterleukin-8RNA, Messenger

Identifiers

PMID23051921
PMCPMC3499332
OpenAlexW2144876374

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.