Cargando…

The effects of 2-hydroxyglutarate on the tumorigenesis of gliomas

Mutation of the isocitrate-dehydrogenase (IDH) enzymes is one of the central research topics regarding gliomagenesis. Indeed, 70% of gliomas are associated with a gain-of-function IDH mutation and consequently synthesize the oncometabolite, 2-hydroxyglutarate (2-HG). This review aims to elucidate th...

Descripción completa

Detalles Bibliográficos
Autores principales: Reiter-Brennan, Cara, Semmler, Lukas, Klein, Andreas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Termedia Publishing House 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377424/
https://www.ncbi.nlm.nih.gov/pubmed/30783384
http://dx.doi.org/10.5114/wo.2018.82642
_version_ 1783395739860205568
author Reiter-Brennan, Cara
Semmler, Lukas
Klein, Andreas
author_facet Reiter-Brennan, Cara
Semmler, Lukas
Klein, Andreas
author_sort Reiter-Brennan, Cara
collection PubMed
description Mutation of the isocitrate-dehydrogenase (IDH) enzymes is one of the central research topics regarding gliomagenesis. Indeed, 70% of gliomas are associated with a gain-of-function IDH mutation and consequently synthesize the oncometabolite, 2-hydroxyglutarate (2-HG). This review aims to elucidate the effects of 2-HG on gliomagenesis. 2-HG promotes tumorigenesis by impacting metabolism, vascularization and altering the epigenome of glioma cells. Glioma metabolism and vascularization is altered by 2-HG’s effect on the stability of hypoxia-inducible factor (HIF) and inhibition of endostatin. However, 2-HG’s impacts on epigenetic mechanisms are more profound to gliomagenesis. Through competitive inhibition of JHDMs and TET proteins, 2-HG orchestrates histone and DNA hypermethylation, which is associated with gene silencing and dedifferentiation of cells. The hypermethylator phenotype induced by 2-HG also results in alterations of the interaction of the immune system with the tumour. Additionally, this study reviews 2-HG promotion of tumorigenesis by inhibiting repair of DNA alkylation damage through competitive inhibition of AlkB proteins.
format Online
Article
Text
id pubmed-6377424
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Termedia Publishing House
record_format MEDLINE/PubMed
spelling pubmed-63774242019-02-19 The effects of 2-hydroxyglutarate on the tumorigenesis of gliomas Reiter-Brennan, Cara Semmler, Lukas Klein, Andreas Contemp Oncol (Pozn) Review Paper Mutation of the isocitrate-dehydrogenase (IDH) enzymes is one of the central research topics regarding gliomagenesis. Indeed, 70% of gliomas are associated with a gain-of-function IDH mutation and consequently synthesize the oncometabolite, 2-hydroxyglutarate (2-HG). This review aims to elucidate the effects of 2-HG on gliomagenesis. 2-HG promotes tumorigenesis by impacting metabolism, vascularization and altering the epigenome of glioma cells. Glioma metabolism and vascularization is altered by 2-HG’s effect on the stability of hypoxia-inducible factor (HIF) and inhibition of endostatin. However, 2-HG’s impacts on epigenetic mechanisms are more profound to gliomagenesis. Through competitive inhibition of JHDMs and TET proteins, 2-HG orchestrates histone and DNA hypermethylation, which is associated with gene silencing and dedifferentiation of cells. The hypermethylator phenotype induced by 2-HG also results in alterations of the interaction of the immune system with the tumour. Additionally, this study reviews 2-HG promotion of tumorigenesis by inhibiting repair of DNA alkylation damage through competitive inhibition of AlkB proteins. Termedia Publishing House 2018-12-31 2018 /pmc/articles/PMC6377424/ /pubmed/30783384 http://dx.doi.org/10.5114/wo.2018.82642 Text en Copyright: © 2018 Termedia Sp. z o. o. http://creativecommons.org/licenses/by-nc-sa/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
spellingShingle Review Paper
Reiter-Brennan, Cara
Semmler, Lukas
Klein, Andreas
The effects of 2-hydroxyglutarate on the tumorigenesis of gliomas
title The effects of 2-hydroxyglutarate on the tumorigenesis of gliomas
title_full The effects of 2-hydroxyglutarate on the tumorigenesis of gliomas
title_fullStr The effects of 2-hydroxyglutarate on the tumorigenesis of gliomas
title_full_unstemmed The effects of 2-hydroxyglutarate on the tumorigenesis of gliomas
title_short The effects of 2-hydroxyglutarate on the tumorigenesis of gliomas
title_sort effects of 2-hydroxyglutarate on the tumorigenesis of gliomas
topic Review Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377424/
https://www.ncbi.nlm.nih.gov/pubmed/30783384
http://dx.doi.org/10.5114/wo.2018.82642
work_keys_str_mv AT reiterbrennancara theeffectsof2hydroxyglutarateonthetumorigenesisofgliomas
AT semmlerlukas theeffectsof2hydroxyglutarateonthetumorigenesisofgliomas
AT kleinandreas theeffectsof2hydroxyglutarateonthetumorigenesisofgliomas
AT reiterbrennancara effectsof2hydroxyglutarateonthetumorigenesisofgliomas
AT semmlerlukas effectsof2hydroxyglutarateonthetumorigenesisofgliomas
AT kleinandreas effectsof2hydroxyglutarateonthetumorigenesisofgliomas