胰腺癌Panc-1细胞microRNA差异表达谱生物信息学的分析

Bioinformatic analysis on the microRNA profiling of pancreatic cancer cell line Panc-1

目的:对胰腺癌细胞差异miRNAs表达谱进行生物信息学分析,以期从整体水平揭示microRNA在胰腺癌癌变和进展中的作用。方法:采用含有924条探针的microRNA微阵列检测胰腺癌Panc-1细胞,以3T3成纤维细胞为对照,筛选Panc-1细胞特异性microRNA表达谱;然后对上调和下调microRNA的靶基因进行Gene Ontology、Pathway和TFBS转录因子结合位点分析,以及构建microRNA和靶基因相互作用网络。结果:与3T3成纤维细胞的microRNA表达谱比较,筛选出9个Panc-1上调microR-NA,20个下调microRNA。TargetScan和mi-Randa软件预测出1 166个microRNA靶基因在Panc-1细胞中上调,212个靶基因下调。以上靶基因在DNA代谢、细胞间信号和胞质溶胶3种GO中富集显著;靶基因共涉及50条信号通路,其中富集度P<0.05的信号通路有6条;转录因子结合位点分析表明,CEBP-β、NF-κB和p53等对于上调以及下调的microRNA可能都有调节作用;microRNA和靶基因的相互作用网络分析表明,HIF-1A等基因连接度高。结论:利用生物信息学方法对胰腺癌细胞microRNA表达谱进行数据分析,可以为进一步了解胰腺癌的发病机制提供新的思路。

OBJECTIVE：To perform bioinformatic anlysis on microRNA profiling of pancreatic cancer cells in order to illustrate the role of microRNA in carcinogenesis and progression in pancreatic cancer. METHODS： The specific microRNA of pancreatic cancer Panc-1 was obtained by a microarray containing 924 probes with 3T3 fibroblast as a control. Then targeted genes of microRNAs were predicted and Gene Ontology, gene network, pathway and Transcription factor binding site （TFBS） analyses were performed. RESULTS： Nine microRNAs were up-regulated in Panc-I cells, and 20 microRNAs were down-regulated. 1 166 up-regulated micro-targeted genes and 212 down-regulated microRNA targeted genes were predicted by TargetScan and miRanda software. For Gene Ontology analysis, the genes involved in DNA metabolism, cell-cell signaling and cytosol were significant. The targeted enes were involved in 10 individual signal pathways, among which 6 had significance with enrichment P value less than 0.05. CEBP-β, NF-κB and p53 were most commonly identified in microRNA TFBS analyses. A panel of genes including HIF-1A bad the most connections with other genes in the constructed gene net-works. CONCLUSION： Bioinformatics provides a useful tool for mining micioRNA profiling of pancreatic cancer cells, and also provides new clues in the understanding of molecular mechanism in pancreatic cancer.