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Epigenetic Bases of Aberrant Glycosylation in Cancer
In this review, the sugar portions of glycoproteins, glycolipids, and glycosaminoglycans constitute the glycome, and the genes involved in their biosynthesis, degradation, transport and recognition are referred to as “glycogenes“. The extreme complexity of the glycome requires the regulatory layer t...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454911/ https://www.ncbi.nlm.nih.gov/pubmed/28481247 http://dx.doi.org/10.3390/ijms18050998 |
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author | Dall’Olio, Fabio Trinchera, Marco |
author_facet | Dall’Olio, Fabio Trinchera, Marco |
author_sort | Dall’Olio, Fabio |
collection | PubMed |
description | In this review, the sugar portions of glycoproteins, glycolipids, and glycosaminoglycans constitute the glycome, and the genes involved in their biosynthesis, degradation, transport and recognition are referred to as “glycogenes“. The extreme complexity of the glycome requires the regulatory layer to be provided by the epigenetic mechanisms. Almost all types of cancers present glycosylation aberrations, giving rise to phenotypic changes and to the expression of tumor markers. In this review, we discuss how cancer-associated alterations of promoter methylation, histone methylation/acetylation, and miRNAs determine glycomic changes associated with the malignant phenotype. Usually, increased promoter methylation and miRNA expression induce glycogene silencing. However, treatment with demethylating agents sometimes results in silencing, rather than in a reactivation of glycogenes, suggesting the involvement of distant methylation-dependent regulatory elements. From a therapeutic perspective aimed at the normalization of the malignant glycome, it appears that miRNA targeting of cancer-deranged glycogenes can be a more specific and promising approach than the use of drugs, which broad target methylation/acetylation. A very specific type of glycosylation, the addition of GlcNAc to serine or threonine (O-GlcNAc), is not only regulated by epigenetic mechanisms, but is an epigenetic modifier of histones and transcription factors. Thus, glycosylation is both under the control of epigenetic mechanisms and is an integral part of the epigenetic code. |
format | Online Article Text |
id | pubmed-5454911 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-54549112017-06-08 Epigenetic Bases of Aberrant Glycosylation in Cancer Dall’Olio, Fabio Trinchera, Marco Int J Mol Sci Review In this review, the sugar portions of glycoproteins, glycolipids, and glycosaminoglycans constitute the glycome, and the genes involved in their biosynthesis, degradation, transport and recognition are referred to as “glycogenes“. The extreme complexity of the glycome requires the regulatory layer to be provided by the epigenetic mechanisms. Almost all types of cancers present glycosylation aberrations, giving rise to phenotypic changes and to the expression of tumor markers. In this review, we discuss how cancer-associated alterations of promoter methylation, histone methylation/acetylation, and miRNAs determine glycomic changes associated with the malignant phenotype. Usually, increased promoter methylation and miRNA expression induce glycogene silencing. However, treatment with demethylating agents sometimes results in silencing, rather than in a reactivation of glycogenes, suggesting the involvement of distant methylation-dependent regulatory elements. From a therapeutic perspective aimed at the normalization of the malignant glycome, it appears that miRNA targeting of cancer-deranged glycogenes can be a more specific and promising approach than the use of drugs, which broad target methylation/acetylation. A very specific type of glycosylation, the addition of GlcNAc to serine or threonine (O-GlcNAc), is not only regulated by epigenetic mechanisms, but is an epigenetic modifier of histones and transcription factors. Thus, glycosylation is both under the control of epigenetic mechanisms and is an integral part of the epigenetic code. MDPI 2017-05-06 /pmc/articles/PMC5454911/ /pubmed/28481247 http://dx.doi.org/10.3390/ijms18050998 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Dall’Olio, Fabio Trinchera, Marco Epigenetic Bases of Aberrant Glycosylation in Cancer |
title | Epigenetic Bases of Aberrant Glycosylation in Cancer |
title_full | Epigenetic Bases of Aberrant Glycosylation in Cancer |
title_fullStr | Epigenetic Bases of Aberrant Glycosylation in Cancer |
title_full_unstemmed | Epigenetic Bases of Aberrant Glycosylation in Cancer |
title_short | Epigenetic Bases of Aberrant Glycosylation in Cancer |
title_sort | epigenetic bases of aberrant glycosylation in cancer |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454911/ https://www.ncbi.nlm.nih.gov/pubmed/28481247 http://dx.doi.org/10.3390/ijms18050998 |
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