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BRD4 regulates self‐renewal ability and tumorigenicity of glioma‐initiating cells by enrichment in the Notch1 promoter region
Bromodomain and extraterminal domain (BET) family proteins are considered to be epigenetic readers that regulate gene expression by recognizing acetyl lysine residues on histones and nonhistone chromatin factors and have been classified as curative targets for a variety of cancers. Glioma‐initiating...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533052/ https://www.ncbi.nlm.nih.gov/pubmed/33135348 http://dx.doi.org/10.1002/ctm2.181 |
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author | Tao, Zhennan Li, Xuetao Wang, Hao Chen, Guangliang Feng, Zibin Wu, Yue Yin, Haoran Zhao, Guozheng Deng, Zhitong Zhao, Chaohui Li, Yanyan Sun, Ting Zhou, Youxin |
author_facet | Tao, Zhennan Li, Xuetao Wang, Hao Chen, Guangliang Feng, Zibin Wu, Yue Yin, Haoran Zhao, Guozheng Deng, Zhitong Zhao, Chaohui Li, Yanyan Sun, Ting Zhou, Youxin |
author_sort | Tao, Zhennan |
collection | PubMed |
description | Bromodomain and extraterminal domain (BET) family proteins are considered to be epigenetic readers that regulate gene expression by recognizing acetyl lysine residues on histones and nonhistone chromatin factors and have been classified as curative targets for a variety of cancers. Glioma‐initiating cells (GICs), which commit self‐renewal, perpetual proliferation, multidirectional differentiation, and vigorous tumorigenicity, sustain the peculiar genetic and epigenetic diversification in the GBM patients, thus, GICs result in tumor recurrence. Abundant evidence demonstrates that BET proteins regulate differentiation of stem cells. However, it endures ambiguous how individual BET proteins take part in GIC advancement, and how do small molecule inhibitors like I‐BET151 target functional autonomous BET proteins. Here, we validated that BRD4, not BRD2 or BRD3, has value in targeted glioma therapy. We announce a signaling pathway concerning BRD4 and Notch1 that sustains the self‐renewal of GICs. Moreover, in‐depth mechanistic research showed that BRD4 was concentrated at the promoter region of Notch1 and may be involved in the process of tumor metabolism. Furthermore, in intracranial models, I‐BET151 eliminated U87 GICs’ tumorigenicity. The outcomes of this research could be conducive to design clinical trials for treatment of glioma based on BRD4. |
format | Online Article Text |
id | pubmed-7533052 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-75330522020-10-05 BRD4 regulates self‐renewal ability and tumorigenicity of glioma‐initiating cells by enrichment in the Notch1 promoter region Tao, Zhennan Li, Xuetao Wang, Hao Chen, Guangliang Feng, Zibin Wu, Yue Yin, Haoran Zhao, Guozheng Deng, Zhitong Zhao, Chaohui Li, Yanyan Sun, Ting Zhou, Youxin Clin Transl Med Research Articles Bromodomain and extraterminal domain (BET) family proteins are considered to be epigenetic readers that regulate gene expression by recognizing acetyl lysine residues on histones and nonhistone chromatin factors and have been classified as curative targets for a variety of cancers. Glioma‐initiating cells (GICs), which commit self‐renewal, perpetual proliferation, multidirectional differentiation, and vigorous tumorigenicity, sustain the peculiar genetic and epigenetic diversification in the GBM patients, thus, GICs result in tumor recurrence. Abundant evidence demonstrates that BET proteins regulate differentiation of stem cells. However, it endures ambiguous how individual BET proteins take part in GIC advancement, and how do small molecule inhibitors like I‐BET151 target functional autonomous BET proteins. Here, we validated that BRD4, not BRD2 or BRD3, has value in targeted glioma therapy. We announce a signaling pathway concerning BRD4 and Notch1 that sustains the self‐renewal of GICs. Moreover, in‐depth mechanistic research showed that BRD4 was concentrated at the promoter region of Notch1 and may be involved in the process of tumor metabolism. Furthermore, in intracranial models, I‐BET151 eliminated U87 GICs’ tumorigenicity. The outcomes of this research could be conducive to design clinical trials for treatment of glioma based on BRD4. John Wiley and Sons Inc. 2020-10-04 /pmc/articles/PMC7533052/ /pubmed/33135348 http://dx.doi.org/10.1002/ctm2.181 Text en © 2020 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Tao, Zhennan Li, Xuetao Wang, Hao Chen, Guangliang Feng, Zibin Wu, Yue Yin, Haoran Zhao, Guozheng Deng, Zhitong Zhao, Chaohui Li, Yanyan Sun, Ting Zhou, Youxin BRD4 regulates self‐renewal ability and tumorigenicity of glioma‐initiating cells by enrichment in the Notch1 promoter region |
title | BRD4 regulates self‐renewal ability and tumorigenicity of glioma‐initiating cells by enrichment in the Notch1 promoter region |
title_full | BRD4 regulates self‐renewal ability and tumorigenicity of glioma‐initiating cells by enrichment in the Notch1 promoter region |
title_fullStr | BRD4 regulates self‐renewal ability and tumorigenicity of glioma‐initiating cells by enrichment in the Notch1 promoter region |
title_full_unstemmed | BRD4 regulates self‐renewal ability and tumorigenicity of glioma‐initiating cells by enrichment in the Notch1 promoter region |
title_short | BRD4 regulates self‐renewal ability and tumorigenicity of glioma‐initiating cells by enrichment in the Notch1 promoter region |
title_sort | brd4 regulates self‐renewal ability and tumorigenicity of glioma‐initiating cells by enrichment in the notch1 promoter region |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533052/ https://www.ncbi.nlm.nih.gov/pubmed/33135348 http://dx.doi.org/10.1002/ctm2.181 |
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