甲基转移酶样3调节食管鳞癌细胞功能的研究
Study on the function of methyltransferase-like 3 in regulating esophageal squamous cell carcinoma cells
熊佳时 1季鹏翔 2王俊婕 2何刚3
作者信息
- 1. 上海市奉贤区中心医院肿瘤内科,上海 201499
- 2. 苏州大学医学院生物化学与分子生物学系
- 3. 上海市奉贤区中心医院胸外科
- 折叠
摘要
目的:探究甲基转移酶样 3(methyltransferase-like 3,METTL3)在食管鳞癌中的表达水平和作用机制.方法:体外构建食管鳞癌细胞Eca-109 的METTL3 敲低模型,利用实时荧光定量PCR(quantitative real-time PCR,qRT-PCR)、Western Blot验证敲低水平,检测肿瘤细胞的增殖、迁移能力.利用差异分析、富集分析以及生存分析等寻找METTL3 的靶基因.结果:敲低METTL3 可以显著抑制食管癌细胞的增殖和迁移能力;利用生物信息学分析寻找到受METTL3 调控的 9 个可能的靶基因(精脒/精胺N1-乙酰基转移酶 1(spermidine/spermine N1-acetyltransferase 1,SAT1)、低密度脂蛋白受体(low density lipoprotein receptor,LDLR)、整合素β1(integrin subunit beta 1,ITGB1)、细胞间黏附分子 5(intercellular adhesion molecule 5,ICAM5)、富含谷氨酸的WD重复序列蛋白 1(glutamate-rich WD40 repeat containing 1,GRWD1)、含纤维连接蛋白Ⅲ型结构域 3A 蛋白(fibronectintype-Ⅲ domain-containing protein 3A,FNDC3A)、DnaJ热休克蛋白家族成员C2[DnaJ heat shock protein family(Hsp40)member C2,DNAJC2]、卷曲螺旋域蛋白 88C(coiled-coil domain containing 88C,CCDC88C)、Rho GTP酶激活蛋白 12(Rho GTPase activating protein 12,ARHGAP12),其中SAT1 高表达与食管鳞癌患者预后不良密切相关,差异有统计学意义.结论:METTL3 在食管鳞癌中发挥促癌作用,可能通过调控SAT1等靶基因的m6A甲基化影响食管鳞癌患者的预后.
Abstract
Objective:To explore the expression levels and mechanisms of methyltransferase-like 3(METTL3)in esophageal squamous cell carcinoma.Methods:In vitro construction of METTL3 knockdown model in Eca-109,validated by quantitative real-time PCR(qRT-PCR)and Western Blot to confirm knockdown levels,and assessment of tumor cell proliferation and migra-tion abilities.Exploring METTL3 target genes through differential analysis,enrichment analysis,and survival analysis.Results:Knocking down METTL3 significantly inhibits the proliferation and migration abilities of esophageal cancer cells.Through bioinformatics analysis,we identified 9 potential target genes regulated by METTL3 spermidine/spermine N1-acetyltransferase 1(SAT1),low density lipoprotein receptor(LDLR),integrin subunit beta 1(ITGB1),intercellular adhesion molecule 5(ICAM5),glutamate-rich WD40 repeat containing 1(GRWD1),fibronectintype-Ⅲ domain-containing protein 3A(FNDC3A),DnaJ heat shock protein family(Hsp40)member C2(DNAJC2),coiled-coil domain containing 88C(CCDC88C),Rho GTPase activating pro-tein 12(ARHGAP12).High expression of SAT1 is closely associated with poor prognosis in esophageal squamous cell carcinoma patients.Conclusions:METTL3 exerts a pro-cancer role in esophageal squamous cell carcinoma,potentially impacting the prognosis of esophageal squamous cell carcinoma patients by regulating m6A methylation of target genes such as SAT1.
关键词
食管鳞癌/甲基转移酶样3/细胞增殖/生存分析Key words
esophageal squamous cell carcinoma/methyltransferase like-3/cell proliferation/survival analysis引用本文复制引用
基金项目
国家自然科学基金面上项目(81872417)
上海市奉贤区科技发展基金(20201411)
上海市奉贤区科技发展基金(20201406)
出版年
2024
NETL
NSTL
万方数据