دورية أكاديمية
أعرض في EDS

Effects of folylpolyglutamate synthase modulation on global and gene-specific DNA methylation and gene expression in human colon and breast cancer cells.

التفاصيل البيبلوغرافية
العنوان: Effects of folylpolyglutamate synthase modulation on global and gene-specific DNA methylation and gene expression in human colon and breast cancer cells.
المؤلفون: Kim SE; Department 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., Hinoue T; Center for Epigenetics, Van Andel Research Institute, Grand Rapids, MI 49503-2518, USA., Kim MS; Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, ON, Canada M5B 1T8., Sohn KJ; 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., Cho RC; Department of Nutritional Sciences, University of Toronto, Toronto, ON, Canada M5S 1A8., Weisenberger DJ; USC 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., Laird PW; Center for Epigenetics, Van Andel Research Institute, Grand Rapids, MI 49503-2518, USA., Kim YI; Department 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.
المصدر: The Journal of nutritional biochemistry [J Nutr Biochem] 2016 Mar; Vol. 29, pp. 27-35. Date of Electronic Publication: 2015 Nov 17.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Validation Study
اللغة: English
بيانات الدورية: Publisher: Elsevier Science Country of Publication: United States NLM ID: 9010081 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4847 (Electronic) Linking ISSN: 09552863 NLM ISO Abbreviation: J Nutr Biochem Subsets: MEDLINE
أسماء مطبوعة: Publication: <1996->: New York, NY : Elsevier Science
Original Publication: Stoneham, MA, USA : Butterworths, c1990-
مواضيع طبية MeSH: Gene Expression Regulation, Neoplastic*, Breast Neoplasms/*genetics , Colonic Neoplasms/*genetics , DNA Methylation/*genetics , Peptide Synthases/*metabolism, Breast Neoplasms/enzymology ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Colonic Neoplasms/enzymology ; Colonic Neoplasms/pathology ; Female ; Humans
مستخلص: 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.
(Copyright © 2015 Elsevier Inc. All rights reserved.)
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معلومات مُعتمدة: P30 CA014089 United States CA NCI NIH HHS; 14126 Canada CAPMC CIHR
فهرسة مساهمة: Keywords: Breast cancer; Colon cancer; DNA methylation; Folate; Folylpolyglutamate synthase (FPGS); Gene expression
المشرفين على المادة: EC 6.3.2.- (Peptide Synthases)
EC 6.3.2.17 (folylpolyglutamate synthetase)
تواريخ الأحداث: Date Created: 20160221 Date Completed: 20161031 Latest Revision: 20200828
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC7450696
DOI: 10.1016/j.jnutbio.2015.10.019
PMID: 26895662
قاعدة البيانات: MEDLINE
الوصف
تدمد:1873-4847
DOI:10.1016/j.jnutbio.2015.10.019