基于circRNA芯片数据的肺癌生物信息学分析

Bioinformatics Analysis of Lung Cancer Based on CircRNA Microarray Data

目的:环状RNA(circRNA)在肿瘤的发展过程中起着重要作用,但具体作用机制并不明确。本文旨在寻找肺癌与癌旁正常组织的差异表达circRNA并预测与其结合的MicroRNA(miRNA)的靶基因。方法:从基因表达数据库(Gene Expression Omnibus,GEO)下载circRNA表达谱数据,芯片GSE101684与GSE112214共包含7例肺癌患者样本与7例肺癌患者癌旁正常样本。首先,利用R软件筛选出样本中差异表达的circRNA;接着,在癌症特异性数据库(Cancer-Specific circRNA Database,CSCD)中找到与差异表达显著的circRNA结合的miRNA;然后,利用Perl编程预测miRNA的靶基因;最后,利用生物学信息手段对靶基因进行基因本体论(Gene Ontology,GO)生物学功能富集分析与京都基因与基因组大百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)信号通路富集分析。结果:共筛选出350个差异表达的circRNA,上调的circRNA有169个,下调的circRNA有181个,其中hsacirc0039908上调最明显。与hsacirc0039908结合的miRNA共有35个,对这些miRNA进行靶基因预测。GO富集分析结果显示与hsacirc0039908结合的miRNA靶基因主要参与肌肉组织发育、对类固醇激素的反应与细胞酰胺代谢过程的负调控等生物学过程。KEGG富集分析结果显示与hsacirc0039908结合的miRNA靶基因主要富集的信号通路有调节干细胞多能性的信号通路、FoxO信号通路与AMPK信号通路等。结论:hsacirc0039908在肺癌组织中显著上调,可能通过与其结合的miRNA间接调控靶基因SOCS7、BTG2与RLF等在肺癌中的作用。

Objective:CircRNAs play important roles in the development of tumors.However,the specific mechanism is not clear.This paper aims to find differentially expressed circRNAs between lung cancer and adjacent normal tissue and predict the target genes of miRNAs that bind to the differentially expressed circRNAs.Methods:CircRNA expression profiles were downloaded from Gene Expression Omnibus.GSE101684 and GSE112214 totally contain 7 samples of lung cancer tissue and 7 samples of adjacent normal tissue.First,R software was used to select differentially expressed circRNAs of the samples.Besides,the miRNAs that bind to significantly differentially expressed circRNAs were found in cancer-specific circRNA database.Perl,a programming language,was then used to predict miRNA target genes.Finally,the target genes were subjected to Gene Ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Results:Among 350 differentially expressed circRNAs,169 up-regulated circRNAs and 181 down-regulated circRNAs were screened,and hsacirc0039908 was up-regulated most significantly.Target genes of 35 miRNAs that bind to hsacirc0039908 were predicted.Results of GO enrichment analysis showed that the target genes of miRNAs combined with hsacirc0039908 were mainly involved in the biological processes such as development of muscle tissue,responses to steroid hormones and negative regulation of cellular amide metabolic process etc.Results of KEGG enrichment analysis showed that target genes of miRNAs combined with hsacirc0039908 were mainly enriched in FoxO,AMPK and signaling pathways regulating pluripotency of stem cells.Conclusion:Hsacirc0039908 is significantly up-regulated in lung cancer tissue and may indirectly regulate the role of target genes,such as SOCS7,BTG2 and RLF,through associative miRNAs.