转录组学联合蛋白质组学分析表皮生长因子样结构域9影响肝癌细胞增殖、侵袭和迁移的信号通路
Transcriptomics combined with proteomics to analyze the signaling pathway of EGFL9 gene affecting the proliferation,invasion and migration of hepatocellular carcinoma
赵陇成 1李子烨 1吴帆 1王百林1
作者信息
- 1. 暨南大学附属广州红十字会医院肝胆外科,广州 510220
- 折叠
摘要
目的 通过转录组学联合蛋白质组学的研究方法,分析表皮生长因子样结构域9(EGFL9)影响肝癌细胞增殖、侵袭和迁移的信号通路.方法 采用RNA干扰技术构建EGFL9基因敲减的Huh-7肝癌细胞系,选取对照组(NC组)和实验组(KD组),每组3个样本,进行转录组学和蛋白质组学分析,筛选出差异基因和差异蛋白质后,对其进行表达关联分析、聚类分析,利用基因本体论(GO)和京都基因和基因组数据库(KEGG)分别进行基因功能和通路的注释富集分析.结果 基于组学分析发现,KD组与NC组比较,有8 335个差异基因,其中上调4 207个,下调4 128个;有298个差异蛋白质,其中上调188个,下调110个.基于两组学联合分析发现,213个共有差异表达基因,其中在转录水平和翻译水平差异表达程度明显的前3名共有差异表达基因为:转铁蛋白受体2(TFR2)、膜联蛋白A1(ANXA1)、溶质载体家族38成员2(LC38A2);共有差异表达基因显著富集的信号通路为:细胞周期信号通路、氨基酸的生物合成通路、p53信号通路和糖酵解/糖异生信号通路.结论 EGFL9可能通过调控TFR2、ANXA1、LC38A2等基因的表达参与肝癌细胞的细胞功能调控,并可能通过调控细胞周期等分子信号通路发挥作用.
Abstract
Objective Transcriptomics combined with proteomics was used to analyze the potential signaling pathways of epidermal growth factor-like domain 9(EGFL9)affecting the proliferation,invasion and migration of hepatocellular carcinoma.Methods RNA interference technique was used to build hepato-cellular carcinoma cell line with EGFL9 Huh-7 gene knockdown,the control group(NC group)and experi-mental group(KD group),each group of three samples,were performed the transcriptome and proteomics analysis,screening differences genes and proteins,to express the correlation analysis,cluster analysis,and subsequently gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)were used for gene function and pathway annotation enrichment analysis,respectively.Results Based on omics analysis,there were 8 335 different genes in KD group compared with NC group,among which 4 207 were up-regulated and 4 128 were down-regulated.There were 298 different proteins,of which 188 were up-regulated and 110 down-regulated.Based on the combined analysis of the two omics,213 differentially expressed genes were found.Among them,the top three common differentially expressed genes at the level of transcription and translation were transferrin receptor 2(TFR2),annexin A1(ANXA1)and solute carrier family 38 member 2(SLC38A2).The common differentially expressed genes were significantly enriched in cell cycle signaling pathway,amino acid biosynthesis pathway,p53 signaling pathway and glycolysis/gluconeogenesis signaling pathway.Conclusion EGFL9 may participate in the regulation of cell function of hepatocellular carcinoma cells by regulating the expression of TFR2,ANXA1,LC38A2 and other genes,and may play a role through the regulation of cell cycle and other molecular signaling pathways.
关键词
癌,肝细胞/转铁蛋白受体2/转录组学/蛋白质组学/细胞周期Key words
Carcinoma,hepatocellular/Transferrin receptor 2/Transcriptomics/Proteomics/Cell cycle引用本文复制引用
基金项目
国家自然科学基金(81974442)
广东省自然科学基金(2020A1515010799)
出版年
2024
NETL
NSTL
万方数据