NOTUM基因抑制肝母细胞瘤迁移和侵袭  

NOTUM gene suppressed hepatoblastoma migration and invasion

作　　者：张雁冰[1] 尹强[1] Zhang Yanbing;Yin Qiang(Department of General Surgery,Hunan Children's Hospital,Changsha 410007,China)

机构地区：[1]湖南省儿童医院普外一科,长沙410007

出　　处：《中华小儿外科杂志》2024年第9期812-818,共7页Chinese Journal of Pediatric Surgery

摘　　要：目的:通过生物信息学筛选验证肝母细胞瘤中异常甲基化和表达的基因并验证其对肿瘤细胞迁移和侵袭的作用。方法:通过生物信息学综合分析GSE81928、GSE75271和GSE78732数据集获得基因甲基化谱和差异表达的基因,并通过STRING数据库和Metascape数据库预测的生物学功能。随后,在肝母细胞瘤组织对筛选的关键基因进行免疫组织化学和蛋白质印迹验证。在HepG2细胞系中对关键基因表达进行敲减以验证其对肿瘤细胞迁移和侵袭的影响。相关分析采用Spearson检验。结果:在肝母细胞瘤中,共筛选出83个异常甲基化和差异表达基因,其主要参与代谢途径和癌症相关途径。后续证实在肝母细胞瘤中AXIN2、LAMB1和NOTUM基因表达上调,SERPINC1基因表达下调。敲减NOTUM表达可显著抑制HepG2细胞的迁移和侵袭。结论:靶向NOTUM基因可抑制肝母细胞瘤细胞的迁移和侵袭,异常甲基化和表达的基因可能作为肝母细胞瘤新的治疗靶点。Objective:To employ bioinformatics to screen and to verify genes with abnormal methylation and expression in hepatoblastoma(HB)and verify their roles in tumor cell migration and invasion.Methods:Gene methylation profiles and differentially expressed genes were obtained by comprehensive bioinformatic analyses of GSE81928,GSE75271 and GSE78732 datasets.And the predicted biological functions were obtained by the databases of STRING and Metascape.Then selected HUB genes(NOTUM)were verified by immunohistochemistry and protein immunoblotting in HB tissue.Knockdown of key gene(NOTUM)expression was performed in HepG 2 cell line for verifying its effect on tumor cell migration and invasion.Spearson's test was utilized for correlation analysis.Results:A total of 83 genes with abnormal methylation and expression were mostly involved in metabolic and cancer-related pathways.AXIN 2,LAMB 1 and NOTUM and SERPINC1 became down-regulated in HB.Knockdown of NOTUM expression significantly suppressed the migration and invasion of HepG 2.Conclusions:Targeting NOTUM gene may suppress the migration and invasion of HB cells.Therefore aberrant methylated and expressed genes may be novel therapeutic targets for HB.

关 键 词：肝母细胞瘤 基因甲基化 肿瘤 迁移 侵袭 

分 类 号：R735.7[医药卫生—肿瘤]