阿霉素诱导下的肝癌细胞HepG2中微小RNA差异表达分析  

Differential Expression Profile Analysis of MicroRNAs in Doxorubicininduced Hepatoma Cell Line HepG2

作　　者：杨亚蓝 郭志云[1] 丁若凡[1] 茆灿泉[1] 郭建秀[1] 熊莉丽[1] 

机构地区：[1]西南交通大学生命科学与工程学院,成都610031

出　　处：《生物技术通报》2016年第6期244-249,共6页Biotechnology Bulletin

基　　金：国家自然科学基金资助项目(31200999);中央高校基本科研业务费专项资金资助(2682013BR022)

摘　　要：旨在研究阿霉素诱导引起的DNA损伤压力下,肝癌细胞Hep G2中参与DNA损伤应答的mi RNA,并分析这些mi RNA靶基因参与肝癌DNA损伤应答相关的生物学进程与通路。通过小RNA测序检测阿霉素处理肝癌细胞Hep G2前后mi RNA的差异表达情况,使用GO与KEGG通路富集方法对差异表达mi RNA靶基因进行功能富集分析。结果显示,共检测出显著表达差异mi RNA 68个,其中上调13个,下调55个。mi RNA靶基因的功能分析结果显示,53条mi RNAs靶基因显著富集于调控细胞增殖、细胞凋亡、细胞迁移和细胞周期等与DNA损伤应答以及肿瘤相关的生物进程和信号通路,包括p53信号通路、癌症通路、Wnt信号通路和MAPK信号通路等。研究表明,在阿霉素诱导下,Hep G2中的差异表达mi RNAs与DNA损伤相关的肿瘤生物学进程以及信号通路显著相关,预示这些mi RNAs在阿霉素引发的肝细胞癌DNA损伤应答中起着重要的作用。The aims of this work are to study the miRNAs of hepatoma cell HepG2 involving in the response to doxorubicin-induced DNA damages,and to analyze the these miRNAs target genes and the biological processes and pathways related to the response to the hepatoma DNA damages. Small RNA sequencing was used to detect the differentially expressed miRNAs between doxorubicin-treated hepatocellular carcinoma cell line HepG2 and untreated one,and the functions of target genes were analyzed by GO（gene ontology）and KEGG pathway enrichment. Remarkably,68 significantly differentially-expressed miRNAs were identified,13 miRNAs were up-regulated and 55 were down-regulated. After the functional analysis of miRNA targets,the 53 miRNAs were enriched in the biological processes of cell proliferation,cell apoptosis, cell invasion and cell cycle arrest,as well as the pathways of p53 signal,cancer,Wnt signal and MPK,etc. The results demonstrate that these differentially-expressed miRNAs are correlated with DNA damage response-related biological processes and signaling pathways, indicating the prominent importance of these miRNAs in the doxorubicin-induced DNA damage response in hepatocellular carcinoma.

关 键 词：阿霉素 肝细胞癌 DNA损伤 小RNA测序 micro RNAS 

分 类 号：R735.7[医药卫生—肿瘤]