[1]王 晴,李亦菲,孙天罕,等.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(01):15-20.[doi:10.3969/j.issn.1671-7414.2026.01.004]
　WANG Qing,LI Yifei,SUN Tianhan,et al.Experimental Study on the Effect and Mechanism of Methyltransferase 3 Inhibitor STM2457 on m6A Expression in HepG2 Human Hepatocellular Carcinoma Cells[J].Journal of Modern Laboratory Medicine,2026,41(01):15-20.[doi:10.3969/j.issn.1671-7414.2026.01.004]
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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()

《现代检验医学杂志》[ISSN:/CN:]

卷:
第41卷
期数:
2026年01期
页码:
15-20
栏目:
论著
出版日期:
2026-01-15

文章信息/Info

Title:
Experimental Study on the Effect and Mechanism of Methyltransferase 3 Inhibitor STM2457 on m6A Expression in HepG2 Human Hepatocellular Carcinoma Cells
文章编号:
1671-7414（2026）01-015-06
作者:
王 晴1a，李亦菲1b，孙天罕1a，刘美兰1a,2，李 童1a,2，曹健夫1a,2，崔红元1a
1.北京医院，国家老年医学中心，中国医学科学院老年医学研究院 a.普通外科，肝胆胰外科；b.临床生物样本管理中心，北京100730；2.北京协和医学院，北京100006
Author(s):
WANG Qing1a，LI Yifei1b，SUN Tianhan1a，LIU Meilan1a，2，LI Tong1a，2，CAO Jianfu1a，2，CUI Hongyuan1a
1a. Department of General Surgery / Department of Hepato-Bilio-Pancreatic Surgery; 1b. Clinical Biobank Center， National Center of Gerontology, Beijing Hospital, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China; 2. Peking Union Medical College Beijing 100006, China
关键词:
甲基转移酶3; STM2457; N6-甲基腺苷; 肝细胞癌
分类号:
R735.7；R730.43
DOI:
10.3969/j.issn.1671-7414.2026.01.004
文献标志码:
A
摘要:
目的?分析甲基转移酶3（METTL3）抑制剂STM2457对人肝癌细胞系HepG2的影响，重点研究其对N6-甲基腺苷（m6A）表达的影响及其抗肿瘤机制。方法将HepG2细胞分为实验组（STM2457处理）和对照组（DMSO处理）。利用纳米孔（Nanopore)测序技术，结合m6Anet，NanoCount，xPore和GFOLD方法，分别对m6A修饰水平、转录组表达及差异基因进行分析。通过基因本体（GO）和京都基因与基因组百科（KEGG）对差异基因进行功能富集分析。结果STM2457降低HepG2细胞的m6A修饰位点数量（6446vs11549）及修饰水平（0.95±0.03vs0.98±0.03），差异具有统计学意义（Z=-19.915，P<0.01）。差异基因分析共筛选出109个上调基因和340个下调基因，其中与肝癌发生发展密切相关的基因PDLIM5、AZGP1和RNASET2，其m6A修饰水平降低，而基因表达水平升高。功能富集分析结果显示，差异基因主要富集在细胞黏附、凋亡、翻译调控及肝细胞癌相关通路。结论STM2457通过抑制METTL3活性，降低HepG2细胞的m6A修饰水平，上调基因PDLIM5，AZGP1和RNASET2的表达，促进HepG2细胞凋亡，为肝癌治疗提供潜在治疗靶点。
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.

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备注/Memo

备注/Memo:
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）。
作者简介：王晴（1999-），女，在读硕士，研究方向：肝细胞癌机制，E-mail：w15809863826@163.com。
通讯作者：崔红元（1983-），男，博士，主任医师，研究方向：肝细胞癌机制，E-mail：cuihongyuan3921@bjhmoh.cn。
更新日期/Last Update: 2026-01-15