现代检验医学杂志2026，Vol.41Issue(1)：15-20,6.DOI:10.3969/j.issn.1671-7414.2026.01.004
甲基转移酶3抑制剂STM2457对人肝癌细胞系HepG2细胞m6A表达影响及机制的实验研究
Experimental Study on the Effect and Mechanism of Methyltransferase 3 Inhibitor STM2457 on m6A Expression in HepG2 Human Hepatocellular Carcinoma Cells
摘要
Abstract
Objective To analyze the mechanism of action of the methyltransferase 3(METTL3)inhibitor STM2457 in human hepatocellular carcinoma(HCC)HepG2 cells,with a focus on its impact on N6-methyladenosine(m6A)modification and its potential as an anti-tumor therapeutic agent.Methods HepG2 cells were divided into an experimental group(treated with STM2457)and a control group(treated with DMSO).Nanopore sequencing technology,combined with m6Anet,NanoCount,xPore,and GFOLD methods,was used to analyze m6A modification levels,transcriptome expression,and differential genes.Functional enrichment analysis of the differential genes was performed using Gene Ontology(GO)and the Kyoto Encyclopedia of Genes and Genomes(KEGG).Results STM2457 reduced the number of m6A sites(6 446 vs 11 549)and modification levels(0.95±0.03 vs 0.98±0.03),and the difference was statistically significant(Z=-19.915,P<0.01)in HepG2 liver cancer cells.Differential gene analysis identified 109 up-regulated genes and 340 down-regulated genes.Among them,the m6A modification of genes closely related to liver cancer progression,including PDLIM5,AZGP1 and RNASET2,was down-regulated,while their gene expression levels were increased.Functional enrichment analysis showed that the differential genes were mainly enriched in cell adhesion,apoptosis,translation regulation and hepatocellular carcinoma-related pathways.Conclusions STM2457 inhibits METTL3 activity reduces m6A modification levels in HepG2 cells,up-regulates the expression of genes PDLIM5,AZGP1 and RNASET2,and promotes apoptosis in HepG2 cells,providing a potential therapeutic target for liver cancer treatment.关键词
甲基转移酶3/STM2457/N6-甲基腺苷/肝细胞癌Key words
methyltransferase 3/STM2457/N6-methyladenosine/hepatocellular carcinoma分类
医药卫生引用本文复制引用
王晴,李亦菲,孙天罕,刘美兰,李童,曹健夫,崔红元..甲基转移酶3抑制剂STM2457对人肝癌细胞系HepG2细胞m6A表达影响及机制的实验研究[J].现代检验医学杂志,2026,41(1):15-20,6.基金项目
北京市优秀人才培养资助计划(青年骨干个人项目)(2018000032600G394). （青年骨干个人项目）
