Linc-RA1 inhibits autophagy and promotes radioresistance by preventing H2Bub1/USP44 combination in glioma cells

Radiotherapy is one of the standard treatments for glioma patients; however, its clinical efficacy is limited by radioresistance. We identified a mechanism of such resistance mediated by linc-RA1 (radioresistance-associated long intergenic noncoding RNA 1). Linc-RA1 was upregulated in radioresistant...

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Autores principales: Zheng, Jieling, Wang, Baiyao, Zheng, Rong, Zhang, Jian, Huang, Chunyue, Zheng, Ronghui, Huang, Zhong, Qiu, Wenze, Liu, Mengzhong, Yang, Kaijun, Mao, Zixu, Ji, Aimin, Yuan, Yawei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492255/
https://www.ncbi.nlm.nih.gov/pubmed/32934196
http://dx.doi.org/10.1038/s41419-020-02977-x
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author Zheng, Jieling
Wang, Baiyao
Zheng, Rong
Zhang, Jian
Huang, Chunyue
Zheng, Ronghui
Huang, Zhong
Qiu, Wenze
Liu, Mengzhong
Yang, Kaijun
Mao, Zixu
Ji, Aimin
Yuan, Yawei
author_facet Zheng, Jieling
Wang, Baiyao
Zheng, Rong
Zhang, Jian
Huang, Chunyue
Zheng, Ronghui
Huang, Zhong
Qiu, Wenze
Liu, Mengzhong
Yang, Kaijun
Mao, Zixu
Ji, Aimin
Yuan, Yawei
author_sort Zheng, Jieling
collection PubMed
description Radiotherapy is one of the standard treatments for glioma patients; however, its clinical efficacy is limited by radioresistance. We identified a mechanism of such resistance mediated by linc-RA1 (radioresistance-associated long intergenic noncoding RNA 1). Linc-RA1 was upregulated in radioresistant glioma cells and glioma tissue samples, compared with radiosensitive cells and nontumor tissues. Linc-RA1 was associated with inferior overall survival and advanced clinical stage of glioma. Linc-RA1 promoted glioma radioresistance in vitro and in vivo. Mechanistically, linc-RA1 stabilized the level of H2B K120 monoubiquitination (H2Bub1) by combining with H2B and inhibiting the interaction between H2Bub1 and ubiquitin-specific protease 44 (USP44), which inhibited autophagy, thus contributing to glioma radioresistance. These results reveal that linc-RA1-mediated autophagy is a key mechanism of radioresistance and is an actionable target for improving radiotherapy efficacy in patients with glioma.
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spelling pubmed-74922552020-10-01 Linc-RA1 inhibits autophagy and promotes radioresistance by preventing H2Bub1/USP44 combination in glioma cells Zheng, Jieling Wang, Baiyao Zheng, Rong Zhang, Jian Huang, Chunyue Zheng, Ronghui Huang, Zhong Qiu, Wenze Liu, Mengzhong Yang, Kaijun Mao, Zixu Ji, Aimin Yuan, Yawei Cell Death Dis Article Radiotherapy is one of the standard treatments for glioma patients; however, its clinical efficacy is limited by radioresistance. We identified a mechanism of such resistance mediated by linc-RA1 (radioresistance-associated long intergenic noncoding RNA 1). Linc-RA1 was upregulated in radioresistant glioma cells and glioma tissue samples, compared with radiosensitive cells and nontumor tissues. Linc-RA1 was associated with inferior overall survival and advanced clinical stage of glioma. Linc-RA1 promoted glioma radioresistance in vitro and in vivo. Mechanistically, linc-RA1 stabilized the level of H2B K120 monoubiquitination (H2Bub1) by combining with H2B and inhibiting the interaction between H2Bub1 and ubiquitin-specific protease 44 (USP44), which inhibited autophagy, thus contributing to glioma radioresistance. These results reveal that linc-RA1-mediated autophagy is a key mechanism of radioresistance and is an actionable target for improving radiotherapy efficacy in patients with glioma. Nature Publishing Group UK 2020-09-15 /pmc/articles/PMC7492255/ /pubmed/32934196 http://dx.doi.org/10.1038/s41419-020-02977-x Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Zheng, Jieling
Wang, Baiyao
Zheng, Rong
Zhang, Jian
Huang, Chunyue
Zheng, Ronghui
Huang, Zhong
Qiu, Wenze
Liu, Mengzhong
Yang, Kaijun
Mao, Zixu
Ji, Aimin
Yuan, Yawei
Linc-RA1 inhibits autophagy and promotes radioresistance by preventing H2Bub1/USP44 combination in glioma cells
title Linc-RA1 inhibits autophagy and promotes radioresistance by preventing H2Bub1/USP44 combination in glioma cells
title_full Linc-RA1 inhibits autophagy and promotes radioresistance by preventing H2Bub1/USP44 combination in glioma cells
title_fullStr Linc-RA1 inhibits autophagy and promotes radioresistance by preventing H2Bub1/USP44 combination in glioma cells
title_full_unstemmed Linc-RA1 inhibits autophagy and promotes radioresistance by preventing H2Bub1/USP44 combination in glioma cells
title_short Linc-RA1 inhibits autophagy and promotes radioresistance by preventing H2Bub1/USP44 combination in glioma cells
title_sort linc-ra1 inhibits autophagy and promotes radioresistance by preventing h2bub1/usp44 combination in glioma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492255/
https://www.ncbi.nlm.nih.gov/pubmed/32934196
http://dx.doi.org/10.1038/s41419-020-02977-x
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