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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. NR₀33928 was identified as an NSUN2-methylated and upregulated lncRNA in GC. Functionally, NR₀33928 upregulated the expression of glutaminase (GLS) by interacting with IGF2BP3/HUR complex to promote GLS mRNA stability. Increased glutamine metabolite, α-KG, upregulated NR₀33928 expression by enhancing its promoter 5-hydroxymethylcytosine (hm5C) demethylation. In conclusion, our results revealed that NSUN2-methylated NR₀33928 promoted GC progression and might be a potential prognostic and therapeutic target for GC.
Fang et al. (Tue,) studied this question.