广泛期与局限期小细胞肺癌差异表达miRNAs的筛选及生物信息学分析  

Screening and bioinformatics analysis of differentially expressed miRNAs between extensive-stage SCLC and limited-stage SCLC

作　　者：薛亚军[1] 耿涛[1] 黄冰[1] 罗波[1] 魏育涛[1] XUE Yajun;GENG Tao;HUANG Bing;LUO Bo;WEI Yutao(The First Affiliated Hospital of Medical School of Shihezi University,Shihezi 832000,China)

机构地区：[1]石河子大学医学院第一附属医院,新疆石河子832000

出　　处：《山东医药》2018年第12期1-4,共4页Shandong Medical Journal

基　　金：国家自然科学基金资助项目(81460059);兵团博士基金资助项目(2014BB019)

摘　　要：目的筛选广泛期与局限期小细胞肺癌(SCLC)间差异表达的miRNAs,分析差异表达miRNAs的靶基因功能。方法从高通量基因表达数据库中下载SCLC转移基因芯片数据GSE67804,采用Qlucore Omics Explorer3.0软件筛选广泛期SCLC(ED组)、局限期SCLC(LD组)患者血清中的差异表达miRNAs,通过生物信息学方法预测差异miRNAs靶基因,并对靶基因进行GO功能富集分析、KEGG信号通路分析以及STRING蛋白互作分析。结果 ED组与LD组筛选出17个差异表达miRNAs(P<0.05,|Fold change|≥2)。生物信息学分析发现,差异miRNAs互补结合的靶基因在胞吞作用、Ras通路、Rap1通路、PI3K-Akt通路、局部黏附等肿瘤相关通路明显富集,靶基因信号传导及转录激活因子(STAT3)、SMAD3、E2F1、基质金属蛋白2(MMP2)、SP1、雄激素受体(AR)、胰岛素样生长因子1受体(IGF1R)、核因子κB1(NFκB1)、蛋白激酶2(AKT2)编码的蛋白在互作网络中具有核心地位。结论广泛期与局限期SCLC间存在17个差异表达miRNAs,这些miRNAs可能通过调控Ras、Rap1、PI3K-Akt等信号通路,进而调节下游靶蛋白参与SCLC转移的发生过程。Objective To screen out the differentially expressed miRNAs between extensive-stage and limited-stage small cell lung cancer(SCLC)and to analyze the function of the targeting gene of differentially expressed miRNAs.Methods The microarray data related to SCLC metastasis were downloaded from the Gene Expression Omnibus(GEO).Qlucore Omics Explorer3.0 software was used to screen out differentially expressed miRNAs between extensive-stage(ED group)and limited-stage SCLC(LD group).Bioinformatics method was used to predict the target genes of differential miRNAs,and the target genes were analyzed with GO enrichment analysis,KEGG pathway analysis,and STRING protein interaction analysis.Results There were 17 differentially expressed miRNAs(P<0.05,|Fold change|≥2)related to SCLC metastasis between ED and LD groups.The bioinformatics results showed that these target genes complementarily binding to miRNAs were enriched in the endocytosis pathway,Ras pathway,Rap1 pathway,PI3K-Akt signaling pathways,Focal adhesion,in which,the key target genes of STAT3,SMAD3,E2F1,MMP2,SP1,AR,IGF1R,NFKB1 and AKT2 played a core role in the interaction network.Conclusion Seventeen differentially expressed miRNAs are found between the extensive-stage and limited-stage SCLC,and the miRNAs may regulate the Ras,Rap1,PI3K-Akt,and other signaling pathways and thus regulate the down-stream target proteins which are involved in the process of SCLC metastasis.

关 键 词：小细胞肺癌 肿瘤转移 微小RNA 生物信息学 基因芯片 

分 类 号：R734.2[医药卫生—肿瘤]