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

作者：Lang Fang, Hongxin Huang, Jialun Lv, Zetian Chen, Lu Chen, Tianlu Jiang, Penghui Xu, Ying Li, Sen Wang, Bowen Li, Li Zheng, Weizhi Wang, Zekuan Xu · 发表于：Cell Death and Disease · 年份：2023 · DOI：10.1038/s41419-023-06049-8 · 被引用次数：106 · 研究领域：RNA modifications and cancer、Cancer-related molecular mechanisms research、Cancer-related gene regulation

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.