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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation / genetics
  • Glutaminase / genetics
  • Glutamine
  • Humans
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Stomach Neoplasms* / genetics
  • Stomach Neoplasms* / metabolism

Substances

  • RNA, Long Noncoding
  • Glutamine
  • Glutaminase
  • RNA, Messenger