m5C-methylated lncRNA NR_033928 promotes gastric cancer proliferation by stabilizing GLS mRNA to promote glutamine metabolism reprogramming

Abnormal 5-methylcytosine (m5C) methylation has been proved to be closely related to gastric carcinogenesis, progression, and prognosis. Dysregulated long noncoding RNAs (lncRNAs) participate in a variety of biological processes in cancer. However, to date, m5C-methylated lncRNAs are rarely research...

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Autores principales: Fang, Lang, Huang, Hongxin, Lv, Jialun, Chen, Zetian, Lu, Chen, Jiang, Tianlu, Xu, Penghui, Li, Ying, Wang, Sen, Li, Bowen, Li, Zheng, Wang, Weizhi, Xu, Zekuan
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/PMC10427642/
https://www.ncbi.nlm.nih.gov/pubmed/37582794
http://dx.doi.org/10.1038/s41419-023-06049-8
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author Fang, Lang
Huang, Hongxin
Lv, Jialun
Chen, Zetian
Lu, Chen
Jiang, Tianlu
Xu, Penghui
Li, Ying
Wang, Sen
Li, Bowen
Li, Zheng
Wang, Weizhi
Xu, Zekuan
author_facet Fang, Lang
Huang, Hongxin
Lv, Jialun
Chen, Zetian
Lu, Chen
Jiang, Tianlu
Xu, Penghui
Li, Ying
Wang, Sen
Li, Bowen
Li, Zheng
Wang, Weizhi
Xu, Zekuan
author_sort Fang, Lang
collection PubMed
description Abnormal 5-methylcytosine (m5C) methylation has been proved to be closely related to gastric carcinogenesis, progression, and prognosis. Dysregulated long noncoding RNAs (lncRNAs) participate in a variety of biological processes in cancer. However, to date, m5C-methylated lncRNAs are rarely researched in gastric cancer (GC). Here, we found that RNA cytosine-C(5)-methyltransferase (NSUN2) was upregulated in GC and high NSUN2 expression was associated with poor prognosis. NR_033928 was identified as an NSUN2-methylated and upregulated lncRNA in GC. Functionally, NR_033928 upregulated the expression of glutaminase (GLS) by interacting with IGF2BP3/HUR complex to promote GLS mRNA stability. Increased glutamine metabolite, α-KG, upregulated NR_033928 expression by enhancing its promoter 5-hydroxymethylcytosine (hm5C) demethylation. In conclusion, our results revealed that NSUN2-methylated NR_033928 promoted GC progression and might be a potential prognostic and therapeutic target for GC.
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spelling pubmed-104276422023-08-17 m5C-methylated lncRNA NR_033928 promotes gastric cancer proliferation by stabilizing GLS mRNA to promote glutamine metabolism reprogramming Fang, Lang Huang, Hongxin Lv, Jialun Chen, Zetian Lu, Chen Jiang, Tianlu Xu, Penghui Li, Ying Wang, Sen Li, Bowen Li, Zheng Wang, Weizhi Xu, Zekuan Cell Death Dis Article Abnormal 5-methylcytosine (m5C) methylation has been proved to be closely related to gastric carcinogenesis, progression, and prognosis. Dysregulated long noncoding RNAs (lncRNAs) participate in a variety of biological processes in cancer. However, to date, m5C-methylated lncRNAs are rarely researched in gastric cancer (GC). Here, we found that RNA cytosine-C(5)-methyltransferase (NSUN2) was upregulated in GC and high NSUN2 expression was associated with poor prognosis. NR_033928 was identified as an NSUN2-methylated and upregulated lncRNA in GC. Functionally, NR_033928 upregulated the expression of glutaminase (GLS) by interacting with IGF2BP3/HUR complex to promote GLS mRNA stability. Increased glutamine metabolite, α-KG, upregulated NR_033928 expression by enhancing its promoter 5-hydroxymethylcytosine (hm5C) demethylation. In conclusion, our results revealed that NSUN2-methylated NR_033928 promoted GC progression and might be a potential prognostic and therapeutic target for GC. Nature Publishing Group UK 2023-08-15 /pmc/articles/PMC10427642/ /pubmed/37582794 http://dx.doi.org/10.1038/s41419-023-06049-8 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
Fang, Lang
Huang, Hongxin
Lv, Jialun
Chen, Zetian
Lu, Chen
Jiang, Tianlu
Xu, Penghui
Li, Ying
Wang, Sen
Li, Bowen
Li, Zheng
Wang, Weizhi
Xu, Zekuan
m5C-methylated lncRNA NR_033928 promotes gastric cancer proliferation by stabilizing GLS mRNA to promote glutamine metabolism reprogramming
title m5C-methylated lncRNA NR_033928 promotes gastric cancer proliferation by stabilizing GLS mRNA to promote glutamine metabolism reprogramming
title_full m5C-methylated lncRNA NR_033928 promotes gastric cancer proliferation by stabilizing GLS mRNA to promote glutamine metabolism reprogramming
title_fullStr m5C-methylated lncRNA NR_033928 promotes gastric cancer proliferation by stabilizing GLS mRNA to promote glutamine metabolism reprogramming
title_full_unstemmed m5C-methylated lncRNA NR_033928 promotes gastric cancer proliferation by stabilizing GLS mRNA to promote glutamine metabolism reprogramming
title_short m5C-methylated lncRNA NR_033928 promotes gastric cancer proliferation by stabilizing GLS mRNA to promote glutamine metabolism reprogramming
title_sort m5c-methylated lncrna nr_033928 promotes gastric cancer proliferation by stabilizing gls mrna to promote glutamine metabolism reprogramming
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10427642/
https://www.ncbi.nlm.nih.gov/pubmed/37582794
http://dx.doi.org/10.1038/s41419-023-06049-8
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