LncRNA INHEG promotes glioma stem cell maintenance and tumorigenicity through regulating rRNA 2’-O-methylation

Glioblastoma (GBM) ranks among the most lethal of human cancers, containing glioma stem cells (GSCs) that display therapeutic resistance. Here, we report that the lncRNA INHEG is highly expressed in GSCs compared to differentiated glioma cells (DGCs) and promotes GSC self-renewal and tumorigenicity...

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Autores principales: Liu, Lihui, Liu, Ziyang, Liu, Qinghua, Wu, Wei, Lin, Peng, Liu, Xing, Zhang, Yuechuan, Wang, Dongpeng, Prager, Briana C., Gimple, Ryan C., Yu, Jichuan, Zhao, Weixi, Wu, Qiulian, Zhang, Wei, Wu, Erzhong, Chen, Xiaomin, Luo, Jianjun, Rich, Jeremy N., Xie, Qi, Jiang, Tao, Chen, Runsheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10657414/
https://www.ncbi.nlm.nih.gov/pubmed/37980347
http://dx.doi.org/10.1038/s41467-023-43113-5
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author Liu, Lihui
Liu, Ziyang
Liu, Qinghua
Wu, Wei
Lin, Peng
Liu, Xing
Zhang, Yuechuan
Wang, Dongpeng
Prager, Briana C.
Gimple, Ryan C.
Yu, Jichuan
Zhao, Weixi
Wu, Qiulian
Zhang, Wei
Wu, Erzhong
Chen, Xiaomin
Luo, Jianjun
Rich, Jeremy N.
Xie, Qi
Jiang, Tao
Chen, Runsheng
author_facet Liu, Lihui
Liu, Ziyang
Liu, Qinghua
Wu, Wei
Lin, Peng
Liu, Xing
Zhang, Yuechuan
Wang, Dongpeng
Prager, Briana C.
Gimple, Ryan C.
Yu, Jichuan
Zhao, Weixi
Wu, Qiulian
Zhang, Wei
Wu, Erzhong
Chen, Xiaomin
Luo, Jianjun
Rich, Jeremy N.
Xie, Qi
Jiang, Tao
Chen, Runsheng
author_sort Liu, Lihui
collection PubMed
description Glioblastoma (GBM) ranks among the most lethal of human cancers, containing glioma stem cells (GSCs) that display therapeutic resistance. Here, we report that the lncRNA INHEG is highly expressed in GSCs compared to differentiated glioma cells (DGCs) and promotes GSC self-renewal and tumorigenicity through control of rRNA 2’-O-methylation. INHEG induces the interaction between SUMO2 E3 ligase TAF15 and NOP58, a core component of snoRNP that guides rRNA methylation, to regulate NOP58 sumoylation and accelerate the C/D box snoRNP assembly. INHEG activation enhances rRNA 2(’)-O-methylation, thereby increasing the expression of oncogenic proteins including EGFR, IGF1R, CDK6 and PDGFRB in glioma cells. Taken together, this study identifies a lncRNA that connects snoRNP-guided rRNA 2’-O-methylation to upregulated protein translation in GSCs, supporting an axis for potential therapeutic targeting of gliomas.
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spelling pubmed-106574142023-11-18 LncRNA INHEG promotes glioma stem cell maintenance and tumorigenicity through regulating rRNA 2’-O-methylation Liu, Lihui Liu, Ziyang Liu, Qinghua Wu, Wei Lin, Peng Liu, Xing Zhang, Yuechuan Wang, Dongpeng Prager, Briana C. Gimple, Ryan C. Yu, Jichuan Zhao, Weixi Wu, Qiulian Zhang, Wei Wu, Erzhong Chen, Xiaomin Luo, Jianjun Rich, Jeremy N. Xie, Qi Jiang, Tao Chen, Runsheng Nat Commun Article Glioblastoma (GBM) ranks among the most lethal of human cancers, containing glioma stem cells (GSCs) that display therapeutic resistance. Here, we report that the lncRNA INHEG is highly expressed in GSCs compared to differentiated glioma cells (DGCs) and promotes GSC self-renewal and tumorigenicity through control of rRNA 2’-O-methylation. INHEG induces the interaction between SUMO2 E3 ligase TAF15 and NOP58, a core component of snoRNP that guides rRNA methylation, to regulate NOP58 sumoylation and accelerate the C/D box snoRNP assembly. INHEG activation enhances rRNA 2(’)-O-methylation, thereby increasing the expression of oncogenic proteins including EGFR, IGF1R, CDK6 and PDGFRB in glioma cells. Taken together, this study identifies a lncRNA that connects snoRNP-guided rRNA 2’-O-methylation to upregulated protein translation in GSCs, supporting an axis for potential therapeutic targeting of gliomas. Nature Publishing Group UK 2023-11-18 /pmc/articles/PMC10657414/ /pubmed/37980347 http://dx.doi.org/10.1038/s41467-023-43113-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Liu, Lihui
Liu, Ziyang
Liu, Qinghua
Wu, Wei
Lin, Peng
Liu, Xing
Zhang, Yuechuan
Wang, Dongpeng
Prager, Briana C.
Gimple, Ryan C.
Yu, Jichuan
Zhao, Weixi
Wu, Qiulian
Zhang, Wei
Wu, Erzhong
Chen, Xiaomin
Luo, Jianjun
Rich, Jeremy N.
Xie, Qi
Jiang, Tao
Chen, Runsheng
LncRNA INHEG promotes glioma stem cell maintenance and tumorigenicity through regulating rRNA 2’-O-methylation
title LncRNA INHEG promotes glioma stem cell maintenance and tumorigenicity through regulating rRNA 2’-O-methylation
title_full LncRNA INHEG promotes glioma stem cell maintenance and tumorigenicity through regulating rRNA 2’-O-methylation
title_fullStr LncRNA INHEG promotes glioma stem cell maintenance and tumorigenicity through regulating rRNA 2’-O-methylation
title_full_unstemmed LncRNA INHEG promotes glioma stem cell maintenance and tumorigenicity through regulating rRNA 2’-O-methylation
title_short LncRNA INHEG promotes glioma stem cell maintenance and tumorigenicity through regulating rRNA 2’-O-methylation
title_sort lncrna inheg promotes glioma stem cell maintenance and tumorigenicity through regulating rrna 2’-o-methylation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10657414/
https://www.ncbi.nlm.nih.gov/pubmed/37980347
http://dx.doi.org/10.1038/s41467-023-43113-5
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