Evidence map›Paper›PMID 25735954›Full record

ArticleCancer immunology research2015

IFNγ Induces DNA Methylation-Silenced GPR109A Expression via pSTAT1/p300 and H3K18 Acetylation in Colon Cancer.

Kankana Bardhan, Amy V Paschall, Dafeng Yang, May R Chen, Priscilla S Simon, Yangzom D Bhutia, Pamela M Martin, Muthusamy Thangaraju, Darren D Browning, Vadivel Ganapathy and 4 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer immunology research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
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

26 citing papers in PubMed, 47 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
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  7. Review
  8. Role of HCAFrontiers in immunology · 2021
    Review
  9. Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Review
  15. Review
  16. Review
  17. Article
  18. Human Gut Microbiota and Gastrointestinal Cancer.Genomics, proteomics & bioinformatics · 2018
    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

14 authors at 1 institution in 1 country.

Kankana BardhanDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia.
Amy V PaschallDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia. Cancer Center, Georgia Regents University, Augusta, Georgia. Charlie Norwood VA Medical Center, Augusta, Georgia.
Dafeng YangDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia. Charlie Norwood VA Medical Center, Augusta, Georgia.
May R ChenDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia.
Priscilla S SimonDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia. Cancer Center, Georgia Regents University, Augusta, Georgia. Charlie Norwood VA Medical Center, Augusta, Georgia.
Yangzom D BhutiaDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia.
Pamela M MartinDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia.
Muthusamy ThangarajuDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia. Cancer Center, Georgia Regents University, Augusta, Georgia.
Darren D BrowningDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia. Cancer Center, Georgia Regents University, Augusta, Georgia.
Vadivel GanapathyDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia. Cancer Center, Georgia Regents University, Augusta, Georgia.
Christopher M HeatonDepartment of Pathology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia.
Keni GuUniversity Hospital, Augusta, Georgia.
Jeffrey R LeeCharlie Norwood VA Medical Center, Augusta, Georgia. Department of Pathology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia.
Kebin LiuDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia. Cancer Center, Georgia Regents University, Augusta, Georgia. Charlie Norwood VA Medical Center, Augusta, Georgia. Kliu@gru.edu.
Augusta University · US

Funding

Role of IRF8 in Tumor Rejection and SuppressionR01CA133085 · NCI · AUGUSTA UNIVERSITY · PI LIU, KEBIN · 2008 to 2019
$2.9M
Molecular basis of inflammation in retina, and novel strategies for limiting itR01EY022704 · NEI · AUGUSTA UNIVERSITY · PI MARTIN, PAMELA M · 2014 to 2018
$2.2M
Role of NF-kB in Fas-mediated Apoptosis and Tumor SuppressionR01CA182518 · NCI · AUGUSTA UNIVERSITY · PI LIU, KEBIN · 2014 to 2018
$1.6M
H3K9 Methylation and Pancreatic Cancer ChemoresistanceR21CA185909 · NCI · AUGUSTA UNIVERSITY · PI LIU, KEBIN · 2014 to 2015
$362k
Function of Verticillin A in Suppression of MDSC and CRC Stem CellsI01BX001962 · VA · CHARLIE NORWOOD VA MEDICAL CENTER · PI LIU, KEBIN · 2014 to 2017
–
BLRD VA I01 BX001962NCI NIH HHS CA133085NCI NIH HHS CA182518NCI NIH HHS R01 CA133085NCI NIH HHS R01 CA182518NCI NIH HHS R21 CA185909NEI NIH HHS R01 EY022704
6 · The paper itself

Abstract

Short-chain fatty acids, metabolites produced by colonic microbiota from fermentation of dietary fiber, act as anti-inflammatory agents in the intestinal tract to suppress proinflammatory diseases. GPR109A is the receptor for short-chain fatty acids. The functions of GPR109A have been the subject of extensive studies; however, the molecular mechanisms underlying GPR109A expression is largely unknown. We show that GPR109A is highly expressed in normal human colon tissues, but is silenced in human colon carcinoma cells. The GPR109A promoter DNA is methylated in human colon carcinoma. Strikingly, we observed that IFNγ, a cytokine secreted by activated T cells, activates GPR109A transcription without altering its promoter DNA methylation. Colon carcinoma grows significantly faster in IFNγ-deficient mice than in wild-type mice in an orthotopic colon cancer mouse model. A positive correlation was observed between GPR109A protein level and tumor-infiltrating T cells in human colon carcinoma specimens, and IFNγ expression level is higher in human colon carcinoma tissues than in normal colon tissues. We further demonstrated that IFNγ rapidly activates pSTAT1 that binds to the promoter of p300 to activate its transcription. p300 then binds to the GPR109A promoter to induce H3K18 hyperacetylation, resulting in chromatin remodeling in the methylated GPR109A promoter. The IFNγ-activated pSTAT1 then directly binds to the methylated but hyperacetylated GPR109 promoter to activate its transcription. Overall, our data indicate that GPR109A acts as a tumor suppressor in colon cancer, and the host immune system might use IFNγ to counteract DNA methylation-mediated GPR109A silencing as a mechanism to suppress tumor development.

Indexed as

AcetylationAnimalsApoptosisCarcinomaCell Line, TumorColonic NeoplasmsDisease Models, AnimalDNA MethylationE1A-Associated p300 ProteinGenes, Tumor SuppressorHumansInterferon-gammaMiceMice, Inbred BALB CMice, KnockoutReceptors, G-Protein-CoupledE1A-Associated p300 ProteinEP300 protein, humanHCAR2 protein, humanInterferon-gammaReceptors, G-Protein-CoupledReceptors, Nicotinic

Identifiers

PMID25735954
PMCPMC4491007
OpenAlexW2059837772

What OpenQuestion holds

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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.