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Targeting HOTAIRM1 ameliorates glioblastoma by disrupting mitochondrial oxidative phosphorylation and serine metabolism

Serine hydroxymethyltransferase 2 (SHMT2), which catalyzes the conversion of serine to glycine and one-carbon transfer reactions in mitochondria, is significantly upregulated in glioblastoma (GBM). However, the mechanism by which the stability of SHMT2 gene expression is maintained to drive GBM tumo...

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Autores principales: Han, Wei, Wang, Shanshan, Qi, Yingjiao, Wu, Fan, Tian, Ningyu, Qiang, Boqin, Peng, Xiaozhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9389257/
https://www.ncbi.nlm.nih.gov/pubmed/35992092
http://dx.doi.org/10.1016/j.isci.2022.104823
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author Han, Wei
Wang, Shanshan
Qi, Yingjiao
Wu, Fan
Tian, Ningyu
Qiang, Boqin
Peng, Xiaozhong
author_facet Han, Wei
Wang, Shanshan
Qi, Yingjiao
Wu, Fan
Tian, Ningyu
Qiang, Boqin
Peng, Xiaozhong
author_sort Han, Wei
collection PubMed
description Serine hydroxymethyltransferase 2 (SHMT2), which catalyzes the conversion of serine to glycine and one-carbon transfer reactions in mitochondria, is significantly upregulated in glioblastoma (GBM). However, the mechanism by which the stability of SHMT2 gene expression is maintained to drive GBM tumorigenesis has not been clarified. Herein, through microarray screening, we identified that HOXA Transcript Antisense RNA, Myeloid-Specific 1 (HOTAIRM1) modulates the SHMT2 level in various GBM cell lines. Serine catabolism and mitochondrial oxidative phosphorylation activities were decreased by HOTAIRM1 inhibition. Mechanistically, according to our mass spectrometry and eCLIP-seq results, HOTAIRM1 can bind to PTBP1 and IGF2BP2. Furthermore, HOTAIRM1 maintains the stability of SHMT2 by promoting the recognition of an m(6)A site and the interaction of PTBP1/IGF2BP2 with SHMT2 mRNA. The stability of HOTAIRM1 can also be enhanced and results in positive feedback regulation to support the progression of GBM. Thus, targeting HOTAIRM1 could be a promising metabolic therapy for GBM.
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spelling pubmed-93892572022-08-20 Targeting HOTAIRM1 ameliorates glioblastoma by disrupting mitochondrial oxidative phosphorylation and serine metabolism Han, Wei Wang, Shanshan Qi, Yingjiao Wu, Fan Tian, Ningyu Qiang, Boqin Peng, Xiaozhong iScience Article Serine hydroxymethyltransferase 2 (SHMT2), which catalyzes the conversion of serine to glycine and one-carbon transfer reactions in mitochondria, is significantly upregulated in glioblastoma (GBM). However, the mechanism by which the stability of SHMT2 gene expression is maintained to drive GBM tumorigenesis has not been clarified. Herein, through microarray screening, we identified that HOXA Transcript Antisense RNA, Myeloid-Specific 1 (HOTAIRM1) modulates the SHMT2 level in various GBM cell lines. Serine catabolism and mitochondrial oxidative phosphorylation activities were decreased by HOTAIRM1 inhibition. Mechanistically, according to our mass spectrometry and eCLIP-seq results, HOTAIRM1 can bind to PTBP1 and IGF2BP2. Furthermore, HOTAIRM1 maintains the stability of SHMT2 by promoting the recognition of an m(6)A site and the interaction of PTBP1/IGF2BP2 with SHMT2 mRNA. The stability of HOTAIRM1 can also be enhanced and results in positive feedback regulation to support the progression of GBM. Thus, targeting HOTAIRM1 could be a promising metabolic therapy for GBM. Elsevier 2022-07-31 /pmc/articles/PMC9389257/ /pubmed/35992092 http://dx.doi.org/10.1016/j.isci.2022.104823 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Han, Wei
Wang, Shanshan
Qi, Yingjiao
Wu, Fan
Tian, Ningyu
Qiang, Boqin
Peng, Xiaozhong
Targeting HOTAIRM1 ameliorates glioblastoma by disrupting mitochondrial oxidative phosphorylation and serine metabolism
title Targeting HOTAIRM1 ameliorates glioblastoma by disrupting mitochondrial oxidative phosphorylation and serine metabolism
title_full Targeting HOTAIRM1 ameliorates glioblastoma by disrupting mitochondrial oxidative phosphorylation and serine metabolism
title_fullStr Targeting HOTAIRM1 ameliorates glioblastoma by disrupting mitochondrial oxidative phosphorylation and serine metabolism
title_full_unstemmed Targeting HOTAIRM1 ameliorates glioblastoma by disrupting mitochondrial oxidative phosphorylation and serine metabolism
title_short Targeting HOTAIRM1 ameliorates glioblastoma by disrupting mitochondrial oxidative phosphorylation and serine metabolism
title_sort targeting hotairm1 ameliorates glioblastoma by disrupting mitochondrial oxidative phosphorylation and serine metabolism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9389257/
https://www.ncbi.nlm.nih.gov/pubmed/35992092
http://dx.doi.org/10.1016/j.isci.2022.104823
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