Evidence map›Paper›PMID 26895662›Full record

ArticleThe Journal of nutritional biochemistry2016

Effects of folylpolyglutamate synthase modulation on 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, Daniel J Weisenberger, Peter W Laird, Young-In Kim

Open access · greenAbstract readValidation Study
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of nutritional biochemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.3field-weighted citation impact, top 37% 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

6 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Review
  3. 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
  4. Review
  5. Article
  6. Nucleic acid biomarkers of β cell stress and death in type 1 diabetes.Current opinion in endocrinology, diabetes, and obesity · 2016
    Review
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

8 authors at 4 institutions in 2 countries.

Sung-Eun KimDepartment of Nutritional Sciences, University of Toronto, Toronto, ON, Canada M5S 1A8; Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, ON, Canada M5B 1T8. Electronic address: sungeun.kim@alum.utoronto.ca.
Toshinori HinoueCenter for Epigenetics, Van Andel Research Institute, Grand Rapids, MI 49503-2518, USA.
Michael S KimKeenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, ON, Canada M5B 1T8.
Kyoung-Jin SohnKeenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, ON, Canada M5B 1T8; Department of Medicine, University of Toronto, Toronto, ON, Canada M5S 1A8.
Robert C ChoDepartment of Nutritional Sciences, University of Toronto, Toronto, ON, Canada M5S 1A8.
Daniel J WeisenbergerUSC Epigenome Center, University of Southern California, Los Angeles, CA 90089-9601, USA; Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, CA 90089-9601, USA.
Peter W LairdCenter for Epigenetics, Van Andel Research Institute, Grand Rapids, MI 49503-2518, USA.
Young-In KimDepartment of Nutritional Sciences, University of Toronto, Toronto, ON, Canada M5S 1A8; Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, ON, Canada M5B 1T8; Department of Medicine, University of Toronto, Toronto, ON, Canada M5S 1A8; Division of Gastroenterology, St. Michael's Hospital, Toronto, ON, Canada M5B 1W8.
University of Toronto · CASt. Michael's Hospital · CAVan Andel Institute · USUniversity of Southern California · US

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Fumito Ito · 1985 to 2026
$181.4M
CIHR 14126NCI NIH HHS P30 CA014089
6 · The paper itself

Abstract

Folylpolyglutamate synthase (FPGS) plays a critical role in intracellular folate homeostasis. FPGS-induced polyglutamylated folates are better substrates for several enzymes involved in the generation of S-adenosylmethionine, the primary methyl group donor, and hence FPGS modulation may affect DNA methylation. DNA methylation is an important epigenetic determinant in gene expression and aberrant DNA methylation is mechanistically linked cancer development. We investigated whether FPGS modulation would affect global and gene-specific promoter DNA methylation with consequent functional effects on gene expression profiles in HCT116 colon and MDA-MB-435 breast cancer cells. Although FPGS modulation altered global DNA methylation and DNA methyltransferases (DNMT) activity, the effects of FPGS modulation on global DNA methylation and DNMT activity could not be solely explained by intracellular folate concentrations and content of long-chain folylpolyglutamates, and it may be cell-specific. FPGS modulation influenced differential gene expression and promoter cytosine-guanine dinucleotide sequences (CpG) DNA methylation involved in cellular development, cell cycle, cell death and molecular transport. Some of the altered gene expression was associated with promoter CpG DNA methylation changes. In both the FPGS-overexpressed HCT116 and MDA-MB-435 cell lines, we identified several differentially expressed genes involved in folate biosynthesis and one-carbon metabolism, which might in part have contributed to the observed increased efficacy of 5-fluorouracil in response to FPGS overexpression. Our data suggest that FPGS modulation affects global and promoter CpG DNA methylation and expression of several genes involved in important biological pathways. The potential role of FPGS modulation in DNA methylation and its associated downstream functional effects warrants further studies.

Indexed as

Gene Expression Regulation, NeoplasticBreast NeoplasmsCell Line, TumorColonic NeoplasmsDNA MethylationFemaleHumansPeptide Synthasesfolylpolyglutamate synthetasePeptide SynthasesBreast cancerColon cancerDNA methylationFolateFolylpolyglutamate synthase (FPGS)Gene expression

Identifiers

PMID26895662
PMCPMC7450696
OpenAlexW2174974954

What OpenQuestion holds

Textmetadata
LicenceTDM
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.