STM2457经YTHDF1/EIF3C抑制Huh-7肝癌细胞增殖  

STM2457 inhibits the proliferation of Huh-7 liver cancer cells through YTHDF1/EIF3C

作　　者：庄家敏 赵培培 杨媛媛 周雨佳 刘栩 SREANG Lyly 涂剑 ZHUANG Jiamin;ZHAO Peipei;YANG Yuanyuan;ZHOU Yujia;LIU Xu;SREANG Lyly;TU Jian(College of Pharmacy,Guilin Medical University,Guilin 541199,China;Guangxi Key Laboratory of Molecular Medicine for Liver Injury and Repair,Guilin 541199,China;College of Basic Medicine,Guilin Medical University,Guilin 541199,China;College of Clinical Medicine,Guilin Medical University,Guilin 541199,China)

机构地区：[1]桂林医学院药学院,桂林541199 [2]广西肝脏损伤与修复分子医学重点实验室,桂林541199 [3]桂林医学院基础医学院,桂林541199 [4]桂林医学院临床医学院,桂林541199

出　　处：《华夏医学》2025年第1期22-27,共6页Acta Medicinae Sinica

基　　金：国家自然科学基金项目(82060662);广西自然科学基金项目(2022JJA140776,2022JJA140639);自治区级大学生创新创业训练计划项目(S202410601137)。

摘　　要：目的探究甲基转移酶3(METTL3)抑制剂STM2457对Huh-7人肝癌细胞增殖能力的作用及其机制。方法经癌症基因组图谱(TCGA)数据库分析METTL3、YTH N^(6)-甲基腺苷RNA结合蛋白1(YTHDF1)、真核起始因子3(EIF3C)和增殖细胞核抗原(PCNA)在肝癌组织与癌旁组织中的表达差异。体外培养Huh-7细胞,先运用CCK8检测不同浓度的STM2457对于Huh-7细胞增殖能力的影响,再通过RT-qPCR检测STM2457对Huh-7细胞中METTL3、YTHDF1、EIF3C、PCNA mRNA表达的影响,进一步通过转染METTL3 siRNA处理后,RT-qPCR检测对Huh-7中METTL3、YTHDF1、EIF3C、PCNA mRNA表达的影响。结果相较于癌旁组织,肝癌组织中增殖标志物PCNA表达显著增强的同时,METTL3、YTHDF1、EIF3C的表达也显著增强;STM2457可显著抑制Huh-7细胞的增殖能力(P<0.01),靶向抑制METTL3表达的同时,还可下调YTHDF1、EIF3C、PCNA的表达;METTL3 siRNA下调METTL3表达的同时,还可同步下调YTHDF1、EIF3C、PCNA的表达。结论STM2457可靶向抑制METTL3的表达,下调YTHDF1、EIF3C、PCNA,进而抑制Huh-7肝癌细胞增殖。Objective To investigate the effect of the methyltransferase 3(METTL3)inhibitor STM2457 on the proliferation ability of Huh-7 human liver cancer cells and its mechanism.Methods The expression differences of METTL3,YTH N^(6)-methyladenosine RNA-binding protein 1(YTHDF1),eukaryotic initiation factor 3(EIF3C),and proliferating cell nuclear antigen(PCNA)in liver cancer tissues and adjacent non-cancerous tissues were analyzed through The Cancer Genome Atlas(TCGA)database.Huh-7 cells were cultured in vitro.Firstly,the CCK8 assay was used to detect the impact of different concentrations of STM2457 on the proliferation ability of Huh-7 cells.Then,RT-qPCR was employed to examine the effects of STM2457 on the mRNA expressions of METTL3,YTHDF1,EIF3C,and PCNA in Huh-7 cells.After further transfection with METTL3 siRNA,RT-qPCR was used to detect the impacts on the mRNA expressions of METTL3,YTHDF1,EIF3C,and PCNA in Huh-7 cells.Results Compared with the adjacent non-cancerous tissues,while the expression of the proliferation marker PCNA was significantly enhanced in liver cancer tissues,the expressions of METTL3,YTHDF1,and EIF3C were also significantly increased.STM2457 could significantly inhibit the proliferation ability of Huh-7 cells(P<0.01).While targeting and inhibiting the expression of METTL3,it could also downregulate the expressions of YTHDF1,EIF3C,and PCNA.When METTL3 siRNA downregulated the expression of METTL3,it could also synchronously downregulate the expressions of YTHDF1,EIF3C,and PCNA.Conclusion STM2457 can target and inhibit METTL3,further downregulate the expression of YTHDF1,EIF3C,and PCNA,and thus inhibit the proliferation of Huh-7 liver cancer cells.

关 键 词：STM2457 甲基转移酶3 YTH N^(6)-甲基腺苷RNA结合蛋白1 真核起始因子3 肝癌增殖 

分 类 号：R735.7[医药卫生—肿瘤]