m(6)A reader IGF2BP2-stabilized CASC9 accelerates glioblastoma aerobic glycolysis by enhancing HK2 mRNA stability

N(6)-methyladenosine (m(6)A) has been identified to exert critical roles in human cancer; however, the regulation of m(6)A modification on glioblastoma multiforme (GBM) and long non-coding RNA (lncRNA) CASC9 (cancer susceptibility 9) is still unclear. Firstly, MeRIP-Seq revealed the m(6)A profile in...

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Autores principales: Liu, Hongjiang, Qin, Shan, Liu, Changqi, Jiang, Le, Li, Chen, Yang, Jiankai, Zhang, Shunyao, Yan, Zhongjie, Liu, Xiaopeng, Yang, Jipeng, Sun, Xiaofeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514511/
https://www.ncbi.nlm.nih.gov/pubmed/34645788
http://dx.doi.org/10.1038/s41420-021-00674-y
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author Liu, Hongjiang
Qin, Shan
Liu, Changqi
Jiang, Le
Li, Chen
Yang, Jiankai
Zhang, Shunyao
Yan, Zhongjie
Liu, Xiaopeng
Yang, Jipeng
Sun, Xiaofeng
author_facet Liu, Hongjiang
Qin, Shan
Liu, Changqi
Jiang, Le
Li, Chen
Yang, Jiankai
Zhang, Shunyao
Yan, Zhongjie
Liu, Xiaopeng
Yang, Jipeng
Sun, Xiaofeng
author_sort Liu, Hongjiang
collection PubMed
description N(6)-methyladenosine (m(6)A) has been identified to exert critical roles in human cancer; however, the regulation of m(6)A modification on glioblastoma multiforme (GBM) and long non-coding RNA (lncRNA) CASC9 (cancer susceptibility 9) is still unclear. Firstly, MeRIP-Seq revealed the m(6)A profile in the GBM. Moreover, the m(6)A-related lncRNA CASC9 expression was significantly elevated in the GBM tissue and its ectopic high expression was associated with poor survival, acting as an independent prognostic factor for GBM patients. Functionally, the aerobic glycolysis was promoted in the CASC9 overexpression transfection, which was inhibited in CASC9 knockdown in GBM cells. Mechanistically, m(6)A reader IGF2BP2 (insulin-like growth factor 2 mRNA binding protein 2) could recognize the m(6)A site of CASC9 and enhance its stability, then CASC9 cooperated with IGF2BP2, forming an IGF2BP2/CASC9 complex, to increase the HK2 (Hexokinase 2) mRNA stability. Our findings reveal that CASC9/IGF2BP2/HK2 axis promotes the aerobic glycolysis of GBM.
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spelling pubmed-85145112021-10-29 m(6)A reader IGF2BP2-stabilized CASC9 accelerates glioblastoma aerobic glycolysis by enhancing HK2 mRNA stability Liu, Hongjiang Qin, Shan Liu, Changqi Jiang, Le Li, Chen Yang, Jiankai Zhang, Shunyao Yan, Zhongjie Liu, Xiaopeng Yang, Jipeng Sun, Xiaofeng Cell Death Discov Article N(6)-methyladenosine (m(6)A) has been identified to exert critical roles in human cancer; however, the regulation of m(6)A modification on glioblastoma multiforme (GBM) and long non-coding RNA (lncRNA) CASC9 (cancer susceptibility 9) is still unclear. Firstly, MeRIP-Seq revealed the m(6)A profile in the GBM. Moreover, the m(6)A-related lncRNA CASC9 expression was significantly elevated in the GBM tissue and its ectopic high expression was associated with poor survival, acting as an independent prognostic factor for GBM patients. Functionally, the aerobic glycolysis was promoted in the CASC9 overexpression transfection, which was inhibited in CASC9 knockdown in GBM cells. Mechanistically, m(6)A reader IGF2BP2 (insulin-like growth factor 2 mRNA binding protein 2) could recognize the m(6)A site of CASC9 and enhance its stability, then CASC9 cooperated with IGF2BP2, forming an IGF2BP2/CASC9 complex, to increase the HK2 (Hexokinase 2) mRNA stability. Our findings reveal that CASC9/IGF2BP2/HK2 axis promotes the aerobic glycolysis of GBM. Nature Publishing Group UK 2021-10-13 /pmc/articles/PMC8514511/ /pubmed/34645788 http://dx.doi.org/10.1038/s41420-021-00674-y Text en © The Author(s) 2021 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, Hongjiang
Qin, Shan
Liu, Changqi
Jiang, Le
Li, Chen
Yang, Jiankai
Zhang, Shunyao
Yan, Zhongjie
Liu, Xiaopeng
Yang, Jipeng
Sun, Xiaofeng
m(6)A reader IGF2BP2-stabilized CASC9 accelerates glioblastoma aerobic glycolysis by enhancing HK2 mRNA stability
title m(6)A reader IGF2BP2-stabilized CASC9 accelerates glioblastoma aerobic glycolysis by enhancing HK2 mRNA stability
title_full m(6)A reader IGF2BP2-stabilized CASC9 accelerates glioblastoma aerobic glycolysis by enhancing HK2 mRNA stability
title_fullStr m(6)A reader IGF2BP2-stabilized CASC9 accelerates glioblastoma aerobic glycolysis by enhancing HK2 mRNA stability
title_full_unstemmed m(6)A reader IGF2BP2-stabilized CASC9 accelerates glioblastoma aerobic glycolysis by enhancing HK2 mRNA stability
title_short m(6)A reader IGF2BP2-stabilized CASC9 accelerates glioblastoma aerobic glycolysis by enhancing HK2 mRNA stability
title_sort m(6)a reader igf2bp2-stabilized casc9 accelerates glioblastoma aerobic glycolysis by enhancing hk2 mrna stability
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514511/
https://www.ncbi.nlm.nih.gov/pubmed/34645788
http://dx.doi.org/10.1038/s41420-021-00674-y
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