基于生物信息学构建肝细胞癌预后相关circRNA-miRNA-mRNA调控网络  

Construction of circRNA-miRNA-mRNA regulatory network related to liver cancer prognosis based on bioinformatics

作　　者：袁浩桐 姜博文 李真鹏 井媛旭 袁硕 杨超 YUAN Haotong;JIANG Bowen;LI Zhenpeng;JING Yuanxu;YUAN Shuo;YANG Chao(School of Stomatology,Qiqihar Medical University,Qiqihar 161006,China;Department of Medical Technology,Qiqihar Medical University,Qiqi­har 161006,China)

机构地区：[1]齐齐哈尔医学院口腔医学院,黑龙江齐齐哈尔161006 [2]齐齐哈尔医学院医学技术学院生物化学教研室,黑龙江齐齐哈尔161006

出　　处：《中国医科大学学报》2023年第5期413-419,共7页Journal of China Medical University

基　　金：黑龙江省卫生健康委2021年医药卫生科研课题(20210202020361);黑龙江省大学生创新创业训练计划项目(202111230007);齐齐哈尔医学科学院项目(QMSI2020B-04)。

摘　　要：目的应用生物信息学方法筛选肝细胞癌中差异表达的环状RNA(circRNA),构建肝癌预后相关circRNA-微RNA(miRNA)-mRNA调控网络。方法从基因表达综合(GEO)数据库中下载肝癌相关circRNA数据集,应用GEO2R工具筛选差异表达circRNA,在Circular RNA Interactome及circBank数据库中预测与circRNA相结合的miRNA,在miRDB、RNAInter及TargetScan数据中预测miRNA的靶基因,构建circRNA-miRNA-mRNA调控网络。应用DAVID软件、STRING数据库、Cytoscape软件及GEPIA数据库对靶基因进行功能注释、通路分析、蛋白质-蛋白质相互作用网络(PPI)构建及预后分析,最后确定肝癌预后相关circRNA-miRNA-核心靶基因调控网络。结果筛选出1个circRNA,为hsa_circRNA_0000301,与之结合的miRNA有4个,分别为hsamiR-377-3p、hsa-miR-767-3p、hsa-miR-1178-3p及hsa-miR-1228-3p。功能注释和通路富集分析显示靶基因主要参与泛素依赖性蛋白质分解代谢等过程,且在MAPK等多个信号通路中显著富集。通过PPI网络及预后分析筛选出3个预后相关核心靶基因,分别为EIF4E、PRKACB和NRAS。最后构建出含有1个circRNA,2个miRNA,3个靶基因的肝癌预后相关调控网络。结论本研究为深入挖掘肝癌发生的分子机制,寻找肝癌潜在的circRNA诊断标志物提供一定的研究依据。Objective To use bioinformatics methods to screen differentially expressed circle RNA(circRNA)in patients with hepatocellular carcinoma(HCC)and to construct a circRNA-microRNA(miRNA)-mRNA regulatory network related to the prognosis of HCC.Methods The HCC-related circRNA datasets were downloaded from the GEO database,differentially expressed circRNAs were screened using the GEO2R tool,and miRNAs bound to circRNAs were predicted in the circRNA Interactome and Circular Bank databases.Target genes of miRNAs were predicted in the miRDB,RNAInter,and TargetScan databases to construct circRNA-miRNA-mRNA regulatory networks.Functional annotation,pathway analysis,protein interaction network construction,and prognostic analysis were performed on target genes using DAVID software,STRING database,Cytoscape software,and GEPIA database,respectively.Finally,circRNA-miRNA-core target gene regulatory network related to liver cancer prognosis was determined.Results One circRNA,hsa_circRNA_0000301,was selected,and four miRNAs were identified:hsa-miR-377-3p,hsa-miR-767-3p,hsa-miR-1178-3p,and hsa-miR-1228-3p.Functional annotation and pathway enrichment analysis showed that target genes were mainly involved in ubiquitin-dependent protein catabolism and were significantly enriched in several signaling pathways,such as MAPK.Three prognostic related core target genes EIF4E,PRKACB,and NRAS were identified using PPI network and prognostic analysis.Finally,a prognostic regulatory network containing one circRNA,two miRNAs,and three target genes was constructed.Conclusion This study provides a basis for further exploration of the molecular mechanism of hepatocellular carcinoma and will guide the search for potential circRNA diagnostic markers for HCC.

关 键 词：肝癌 环状RNA 微RNA 竞争性内源RNA 

分 类 号：R735.7[医药卫生—肿瘤]