脂肪量和肥胖相关蛋白FTO调控IFIT2促进肝细胞癌发生发展
FTO promotes the development of hepatocellular carcinoma via regulating IFIT2
兰兰 1宣自学 1姜金颖1
作者信息
- 1. 浙江省人民医院(杭州医学院附属人民医院)临床药学中心药学部,杭州 310014
- 折叠
摘要
目的 初步研究脂肪量和肥胖相关蛋白(FTO)调控肝细胞癌(HCC)的分子机制.方法 构建FTO敲低的肝细胞癌细胞系HepG2细胞,收集FTO敲低的和未敲低的HepG2细胞,利用Illumina Hiseq平台进行高通量测序,筛选两组别间基因表达差异;通过对这些差异基因进行GO和KEGG富集分析,研究FTO调控通路及筛选FTO下游靶基因;利用生信分析和细胞实验揭示FTO下游靶基因在HCC中的作用.结果 转录组测序结果显示,FTO敲低的和未敲低的HepG2细胞间有386个基因发生了差异性表达,它们参与对干扰素-γ的反应等生物过程;FTO敲低后IFIT2(响应性最强的干扰素刺激基因之一)表达上调;IFIT2多个位点会发生潜在的m6 A甲基化;IFIT2高表达HCC患者生存期显著延长,敲低IFIT2促进HCC生长和迁移.结论 FTO可能通过介导m6 A调控IFIT2,进而促进HCC发生发展.
Abstract
Objective To study the molecular mechanism of fat mass and obesity-associated protein (FTO) regula-ting hepatocellular carcinoma (HCC).Methods HepG2 cells of knock-down FTO were constructed, HepG2 cells of knock-down FTO and HepG2 cells were collected, and high-throughput sequencing was performed using Illumina Hiseq platform to screen the gene expression differences between the two groups.Through GO and KEGG enrich-ment analysis of these differential genes, FTO regulatory pathways were studied and downstream target genes of FTO were screened.The role of FTO downstream target gene in HCC was revealed by bioinformatic analysis and cell ex-periments.Results Transcriptome sequencing showed that386 genes were differentially expressed between HepG2 cells of knock-down FTO and HepG2 cells, and they were involved in biological processes such as response to inter-feron-gamma.The expression of IFIT2, one of the most responsive interferon-stimulating genes, was up-regulated after FTO knockdown.Potential m6 A methylation occurred at multiple sites of IFIT2.The survival of HCC patients with high expression of IFIT2 was significantly prolonged, and knock-down of IFIT2 promoted the growth and migra-tion of HepG2 cells.Conclusion FTO may regulate IFIT2 by mediating m6A, and further promote the occurrence and development of HCC.
关键词
FTO/IFIT2/肝细胞癌/转录组测序/HepG2/m6AKey words
FTO/IFIT2/hepatocellular carcinoma/transcriptome sequencing/HepG2/m6A引用本文复制引用
基金项目
浙江省公益技术应用研究计划项目(LYY21H-310008)
浙江省医药卫生科技计划项目(2022KY060)
浙江省医药卫生科技计划项目(2023KY459)
浙江省医药卫生科技计划项目(2023KY524)
出版年
2024
国家科技期刊平台
NSTL
万方数据