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Aberrant Transcriptional Regulation of Super-enhancers by RET Finger Protein-histone Deacetylase 1 Complex in Glioblastoma: Chemoresistance to Temozolomide
Glioblastoma (GBM), the most common primary brain tumor, is the most aggressive human cancers, with a median survival rate of only 14.6 months. Temozolomide (TMZ) is the frontline chemotherapeutic drug in GBM. Drug resistance is the predominant obstacle in TMZ therapy. Drug resistance occurs via mul...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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The Japan Neurosurgical Society
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6694022/ https://www.ncbi.nlm.nih.gov/pubmed/31178471 http://dx.doi.org/10.2176/nmc.ra.2019-0049 |
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author | NATSUME, Atsushi HIRANO, Masaki RANJIT, Melissa AOKI, Kosuke WAKABAYASHI, Toshihiko |
author_facet | NATSUME, Atsushi HIRANO, Masaki RANJIT, Melissa AOKI, Kosuke WAKABAYASHI, Toshihiko |
author_sort | NATSUME, Atsushi |
collection | PubMed |
description | Glioblastoma (GBM), the most common primary brain tumor, is the most aggressive human cancers, with a median survival rate of only 14.6 months. Temozolomide (TMZ) is the frontline chemotherapeutic drug in GBM. Drug resistance is the predominant obstacle in TMZ therapy. Drug resistance occurs via multiple pathways such as DNA mismatch repair and base excision repair systems, by which glioma cells acquire chemoresistance to some extent (5% and 95%, respectively). Histone3 Lysin27 residue-acetylation (H3K27ac) status regulates cis-regulatory elements, which increases the likelihood of gene transcription. Histone deacetylase (HDAC) complex deacetylate lysine residues on core histones, leading to a decrease in gene transcription. In cis-regulatory element regions, complexes with HDAC repress histones by H3K27ac deacetylation. The cis-regulating and three-dimensional transcriptional mechanism is called “super-enhancer”. RET finger protein (RFP) is a protein that is expressed in many kinds of cancer. RFP forms a protein complex with HDAC1. The disruption of the RFP–HDAC1 complex has resulted in increased drug sensitivity in other cancers. We conclude that the downregulation of RFP or the disruption of the RFP/HDAC1 complex leads to an increase in TMZ efficacy in glioblastoma by changing histone modifications which lead to changes in cell division, cell cycle and apoptosis. |
format | Online Article Text |
id | pubmed-6694022 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | The Japan Neurosurgical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-66940222019-08-15 Aberrant Transcriptional Regulation of Super-enhancers by RET Finger Protein-histone Deacetylase 1 Complex in Glioblastoma: Chemoresistance to Temozolomide NATSUME, Atsushi HIRANO, Masaki RANJIT, Melissa AOKI, Kosuke WAKABAYASHI, Toshihiko Neurol Med Chir (Tokyo) Review Article Glioblastoma (GBM), the most common primary brain tumor, is the most aggressive human cancers, with a median survival rate of only 14.6 months. Temozolomide (TMZ) is the frontline chemotherapeutic drug in GBM. Drug resistance is the predominant obstacle in TMZ therapy. Drug resistance occurs via multiple pathways such as DNA mismatch repair and base excision repair systems, by which glioma cells acquire chemoresistance to some extent (5% and 95%, respectively). Histone3 Lysin27 residue-acetylation (H3K27ac) status regulates cis-regulatory elements, which increases the likelihood of gene transcription. Histone deacetylase (HDAC) complex deacetylate lysine residues on core histones, leading to a decrease in gene transcription. In cis-regulatory element regions, complexes with HDAC repress histones by H3K27ac deacetylation. The cis-regulating and three-dimensional transcriptional mechanism is called “super-enhancer”. RET finger protein (RFP) is a protein that is expressed in many kinds of cancer. RFP forms a protein complex with HDAC1. The disruption of the RFP–HDAC1 complex has resulted in increased drug sensitivity in other cancers. We conclude that the downregulation of RFP or the disruption of the RFP/HDAC1 complex leads to an increase in TMZ efficacy in glioblastoma by changing histone modifications which lead to changes in cell division, cell cycle and apoptosis. The Japan Neurosurgical Society 2019-08 2019-06-07 /pmc/articles/PMC6694022/ /pubmed/31178471 http://dx.doi.org/10.2176/nmc.ra.2019-0049 Text en © 2019 The Japan Neurosurgical Society This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/ |
spellingShingle | Review Article NATSUME, Atsushi HIRANO, Masaki RANJIT, Melissa AOKI, Kosuke WAKABAYASHI, Toshihiko Aberrant Transcriptional Regulation of Super-enhancers by RET Finger Protein-histone Deacetylase 1 Complex in Glioblastoma: Chemoresistance to Temozolomide |
title | Aberrant Transcriptional Regulation of Super-enhancers by RET Finger Protein-histone Deacetylase 1 Complex in Glioblastoma: Chemoresistance to Temozolomide |
title_full | Aberrant Transcriptional Regulation of Super-enhancers by RET Finger Protein-histone Deacetylase 1 Complex in Glioblastoma: Chemoresistance to Temozolomide |
title_fullStr | Aberrant Transcriptional Regulation of Super-enhancers by RET Finger Protein-histone Deacetylase 1 Complex in Glioblastoma: Chemoresistance to Temozolomide |
title_full_unstemmed | Aberrant Transcriptional Regulation of Super-enhancers by RET Finger Protein-histone Deacetylase 1 Complex in Glioblastoma: Chemoresistance to Temozolomide |
title_short | Aberrant Transcriptional Regulation of Super-enhancers by RET Finger Protein-histone Deacetylase 1 Complex in Glioblastoma: Chemoresistance to Temozolomide |
title_sort | aberrant transcriptional regulation of super-enhancers by ret finger protein-histone deacetylase 1 complex in glioblastoma: chemoresistance to temozolomide |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6694022/ https://www.ncbi.nlm.nih.gov/pubmed/31178471 http://dx.doi.org/10.2176/nmc.ra.2019-0049 |
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