基于外泌体exoRBase2.0数据库构建肝细胞癌相关的ceRNA网络并进行相关分析  

Construction and analysis of hepatocellular carcinoma competing endogenous RNA network based on exosomal exoRBase2.0 database

作　　者：任佳怡 陈赞豪 李杨 史芸芩 凌宇婧 周鹭[2] REN Jiayi;CHEN Zanhao;LI Yang;SHI Yunqin;LING Yujing;ZHOU Lu(Xinglin College,Nantong University,Nantong 226001,Jiangsu,China;the Affiliated Hospital of Nantong University,Nantong 226001,Jiangsu,China)

机构地区：[1]南通大学杏林学院,江苏南通226001 [2]南通大学附属医院,江苏南通226001

出　　处：《右江民族医学院学报》2024年第3期328-335,共8页Journal of Youjiang Medical University for Nationalities

基　　金：江苏省大学生创新创业训练计划资助项目(202313993062xl)。

摘　　要：目的基于生物大数据构建肝细胞癌(HCC)患者血液外泌体竞争性内源RNA(ceRNA)调控网络,并对HCC发病机制进行探究。方法从exoRBase 2.0数据库中下载HCC患者和正常人群血液外泌体基因测序数据,并应用R语言进行差异分析。通过TargetScan、miRanda、starBase和miRcode数据库预测与mRNA、lncRNA、circRNA结合的miRNA并对其进行差异表达分析,将结果导入Cytoscape软件,构建ceRNA网络,进一步对其进行GO和KEGG富集分析,并使用CytoHubba插件筛选核心基因。将核心基因导入UALCAN和Kaplan-Meier Plotter网站进行基因表达量和生存分析;并通过TIMER2.0网站进行免疫浸润分析。结果GO分析显示富集在骨髓细胞分化和横纹肌细胞分化等功能,KEGG分析显示富集在催产素信号通路和cGMP-PKG信号通路,生存分析显示CELF2高表达组HCC患者的生存率显著高于低表达组;免疫浸润分析显示CELF2的高表达与HCC患者的肿瘤纯度显著呈负相关,与多种免疫细胞显著呈正相关。结论本研究成功构建了HCC患者血液外泌体ceRNA调控网络,从分子层面阐述了HCC的发生、转移和侵袭机制,为HCC的临床诊疗提供理论支持。Objective To construct the competitive endogenous RNA(ceRNA)regulatory network of blood exosomes in patients with hepatocellular carcinoma(HCC)based on biological big data,and to explore the pathogenesis of HCC.Methods The gene sequencing data of blood exosomes from HCC patients and normal individuals were downloaded from the exoRBase 2.0 database,and differential analysis was performed using R language.TargetScan,miRanda starBase databases and miRcode were utilized to predict miRNAs binding to mRNA,lncRNA and circRNA,and analyze their differential expression.Subsequently,the results were imported into Cytoscape software to construct the ceRNA network.Furthermore,GO and KEGG enrichment analyses were conducted,and the core genes were screened by CytoHubba plugin.The core genes were then imported into the UALCAN and Kaplan-Meier Plotter websites for gene expression and survival analysis.Additionally,TIMER2.0 website was used to analyze the immune infiltration.Results The GO analysis showed enrichment in bone marrow cell differentiation and striated muscle cell differentiation.The KEGG analysis demonstrated enrichment in the oxytocin signaling pathway and the cGMP-PKG signaling pathway.Survival analysis indicated that HCC patients with high CELF2 expression had significantly higher survival rates compared to those with low CELF2 expression.Immune infiltration analysis showed that high CELF2 expression was significantly negatively correlated with tumor purity and positively correlated with various immune cells in HCC patients.Conclusion This study successfully constructed the ceRNA regulatory network of blood exosomes from HCC patients,elucidating the molecular mechanisms underlying the occurrence,metastasis and invasion of HCC.These findings provide theoretical support for the clinical diagnosis and treatment of HCC.

关 键 词：肝细胞癌 外泌体 竞争性内源RNA 生物信息学 

分 类 号：R735.7[医药卫生—肿瘤]