Evidence map›Paper›PMID 25502219›Full record

ArticleGenes & nutrition2015

γ-Glutamyl hydrolase modulation significantly influences global and gene-specific DNA methylation and gene expression in human colon and breast cancer cells.

Sung-Eun Kim, Toshinori Hinoue, Michael S Kim, Kyoung-Jin Sohn, Robert C Cho, Peter D Cole, Daniel J Weisenberger, Peter W Laird, Young-In Kim

Open access · bronzeAbstract read
In one paragraph

Article in Genes & nutrition, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.6field-weighted citation impact, top 34% 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

11 citing papers in PubMed, 13 citations in OpenAlex.

  1. Plasma proteomic signatures improve risk stratification and personalized screening for gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2026
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  5. Article
  6. Review
  7. Elimination of human folypolyglutamate synthetase alters programming and plasticity of somatic cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019
    Article
  8. Review
  9. Article
  10. Article
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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 5 institutions in 2 countries.

Sung-Eun KimDepartment of Nutritional Sciences, University of Toronto, Toronto, ON, M5S 1A8, Canada, sungeun.kim@alum.utoronto.ca.
Toshinori Hinoue
Michael S Kim
Kyoung-Jin Sohn
Robert C Cho
Peter D Cole
Daniel J Weisenberger
Peter W Laird
Young-In Kim
University of Toronto · CAVan Andel Institute · USAlbert Einstein College of Medicine · USSt. Michael's Hospital · CAUniversity of Southern California · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

γ-Glutamyl hydrolase (GGH) plays an important role in folate homeostasis by catalyzing hydrolysis of polyglutamylated folate into monoglutamates. Polyglutamylated folates are better substrates for several enzymes involved in the generation of S-adenosylmethionine, the primary methyl group donor, and hence, GGH modulation may affect DNA methylation. DNA methylation is an important epigenetic determinant in gene expression, in the maintenance of DNA integrity and stability, and in chromatin modifications, and aberrant or dysregulation of DNA methylation has been mechanistically linked to the development of human diseases including cancer. Using a recently developed in vitro model of GGH modulation in HCT116 colon and MDA-MB-435 breast cancer cells, we investigated whether GGH modulation would affect global and gene-specific DNA methylation and whether these alterations were associated with significant gene expression changes. In both cell lines, GGH overexpression decreased global DNA methylation and DNA methyltransferase (DNMT) activity, while GGH inhibition increased global DNA methylation and DNMT activity. Epigenomic and gene expression analyses revealed that GGH modulation influenced CpG promoter DNA methylation and gene expression involved in important biological pathways including cell cycle, cellular development, and cellular growth and proliferation. Some of the observed altered gene expression appeared to be regulated by changes in CpG promoter DNA methylation. Our data suggest that the GGH modulation-induced changes in total intracellular folate concentrations and content of long-chain folylpolyglutamates are associated with functionally significant DNA methylation alterations in several important biological pathways.

Identifiers

PMID25502219
PMCPMC4265218
OpenAlexW2003340282

What OpenQuestion holds

Textmetadata
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.