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

  • Cell Death Dis. 2023 Aug 15;14(8):520. doi: 10.1038/s41419-023-06049-8.
Lang Fang  #  1 ,  Hongxin Huang  #  1 ,  Jialun Lv  #  1 ,  Zetian Chen  #  1 ,  Chen Lu  1 ,  Tianlu Jiang  1 ,  Penghui Xu  1 ,  Ying Li  1 ,  Sen Wang  1 ,  Bowen Li  1 ,  Zheng Li  1 ,  Weizhi Wang  2 ,  Zekuan Xu  3  4
Affiliations
  • 1. Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
  • 2. Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China. [email protected].
  • 3. Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China. [email protected].
  • 4. Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, 210029, Nanjing, Jiangsu Province, China. [email protected].
  • # Contributed equally.
PMID: 37582794 DOI: 10.1038/s41419-023-06049-8
Abstract

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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