METTL3-mediated m6A modification of LINC00839 maintains glioma stem cells and radiation resistance by activating Wnt/β-catenin signaling

Long noncoding RNAs (lncRNAs) are involved in glioma initiation and progression. Glioma stem cells (GSCs) are essential for tumor initiation, maintenance, and therapeutic resistance. However, the biological functions and underlying mechanisms of lncRNAs in GSCs remain poorly understood. Here, we ide...

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Autores principales: Yin, Jianxing, Ding, Fangshu, Cheng, Zhangchun, Ge, Xin, Li, Yanhui, Zeng, Ailiang, Zhang, Junxia, Yan, Wei, Shi, Zhumei, Qian, Xu, You, Yongping, Ding, Zhiliang, Ji, Jing, Wang, Xiefeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10338500/
https://www.ncbi.nlm.nih.gov/pubmed/37438359
http://dx.doi.org/10.1038/s41419-023-05933-7
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author Yin, Jianxing
Ding, Fangshu
Cheng, Zhangchun
Ge, Xin
Li, Yanhui
Zeng, Ailiang
Zhang, Junxia
Yan, Wei
Shi, Zhumei
Qian, Xu
You, Yongping
Ding, Zhiliang
Ji, Jing
Wang, Xiefeng
author_facet Yin, Jianxing
Ding, Fangshu
Cheng, Zhangchun
Ge, Xin
Li, Yanhui
Zeng, Ailiang
Zhang, Junxia
Yan, Wei
Shi, Zhumei
Qian, Xu
You, Yongping
Ding, Zhiliang
Ji, Jing
Wang, Xiefeng
author_sort Yin, Jianxing
collection PubMed
description Long noncoding RNAs (lncRNAs) are involved in glioma initiation and progression. Glioma stem cells (GSCs) are essential for tumor initiation, maintenance, and therapeutic resistance. However, the biological functions and underlying mechanisms of lncRNAs in GSCs remain poorly understood. Here, we identified that LINC00839 was overexpressed in GSCs. A high level of LINC00839 was associated with GBM progression and radiation resistance. METTL3-mediated m6A modification on LINC00839 enhanced its expression in a YTHDF2-dependent manner. Mechanistically, LINC00839 functioned as a scaffold promoting c-Src-mediated phosphorylation of β-catenin, thereby inducing Wnt/β-catenin activation. Combinational use of celecoxib, an inhibitor of Wnt/β-catenin signaling, greatly sensitized GSCs to radiation. Taken together, our results showed that LINC00839, modified by METTL3-mediated m6A, exerts tumor progression and radiation resistance by activating Wnt/β-catenin signaling.
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spelling pubmed-103385002023-07-14 METTL3-mediated m6A modification of LINC00839 maintains glioma stem cells and radiation resistance by activating Wnt/β-catenin signaling Yin, Jianxing Ding, Fangshu Cheng, Zhangchun Ge, Xin Li, Yanhui Zeng, Ailiang Zhang, Junxia Yan, Wei Shi, Zhumei Qian, Xu You, Yongping Ding, Zhiliang Ji, Jing Wang, Xiefeng Cell Death Dis Article Long noncoding RNAs (lncRNAs) are involved in glioma initiation and progression. Glioma stem cells (GSCs) are essential for tumor initiation, maintenance, and therapeutic resistance. However, the biological functions and underlying mechanisms of lncRNAs in GSCs remain poorly understood. Here, we identified that LINC00839 was overexpressed in GSCs. A high level of LINC00839 was associated with GBM progression and radiation resistance. METTL3-mediated m6A modification on LINC00839 enhanced its expression in a YTHDF2-dependent manner. Mechanistically, LINC00839 functioned as a scaffold promoting c-Src-mediated phosphorylation of β-catenin, thereby inducing Wnt/β-catenin activation. Combinational use of celecoxib, an inhibitor of Wnt/β-catenin signaling, greatly sensitized GSCs to radiation. Taken together, our results showed that LINC00839, modified by METTL3-mediated m6A, exerts tumor progression and radiation resistance by activating Wnt/β-catenin signaling. Nature Publishing Group UK 2023-07-12 /pmc/articles/PMC10338500/ /pubmed/37438359 http://dx.doi.org/10.1038/s41419-023-05933-7 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
Yin, Jianxing
Ding, Fangshu
Cheng, Zhangchun
Ge, Xin
Li, Yanhui
Zeng, Ailiang
Zhang, Junxia
Yan, Wei
Shi, Zhumei
Qian, Xu
You, Yongping
Ding, Zhiliang
Ji, Jing
Wang, Xiefeng
METTL3-mediated m6A modification of LINC00839 maintains glioma stem cells and radiation resistance by activating Wnt/β-catenin signaling
title METTL3-mediated m6A modification of LINC00839 maintains glioma stem cells and radiation resistance by activating Wnt/β-catenin signaling
title_full METTL3-mediated m6A modification of LINC00839 maintains glioma stem cells and radiation resistance by activating Wnt/β-catenin signaling
title_fullStr METTL3-mediated m6A modification of LINC00839 maintains glioma stem cells and radiation resistance by activating Wnt/β-catenin signaling
title_full_unstemmed METTL3-mediated m6A modification of LINC00839 maintains glioma stem cells and radiation resistance by activating Wnt/β-catenin signaling
title_short METTL3-mediated m6A modification of LINC00839 maintains glioma stem cells and radiation resistance by activating Wnt/β-catenin signaling
title_sort mettl3-mediated m6a modification of linc00839 maintains glioma stem cells and radiation resistance by activating wnt/β-catenin signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10338500/
https://www.ncbi.nlm.nih.gov/pubmed/37438359
http://dx.doi.org/10.1038/s41419-023-05933-7
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