【摘要】 目的运用生物信息学方法研究复发转移乳腺癌组织中的差异表达MicroRNAs,预测其在乳腺癌预后中的分子调控网络。方法从GEO数据库中获取乳腺癌组织Mi RNA表达谱,包括131例10年内无远处转移复发者,79例10年内有复发者。GEO2R在线分析工具筛选差异表达MiRNA,靶基因预测验证数据库预测miRNA靶基因,使用DAVID工具的基因功能注释和通路富集方法对靶基因进行分析。TF-miRNA调控数据库寻找其上游转录因子,Cytoscape软件构建互作网络。结果复发转移组乳腺癌组织共筛选到差异表达的mi RNA 5个,其中表达上调3个,表达下调2个。得到4个相关上游转录因子HIF1A、EGR1、FOXM1、ESR2,与差异miRNA共调控154个的靶基因。靶基因功能集中在BMP信号通路,TGF-β信号通路,细胞骨架组装功能和Rho GTPases信号通路。结论差异性表达的mRNA包括hsa-miR-210、hsa-miR-33a、hsa-miR-32、hsa-miR-135a、hsa-miR-30a-3p,利用生物信息学方法,能够有效获取信息,为乳腺癌的治疗及预后监测的新策略研究开辟新思路。更多还原

【Abstract】 Objective To explore changes in the expression of MicroRNAs related to prognosis in breast cancer tissue. Methods Microarray data of breast cancer tissue were downloaded from the GEO database,including Micro RNAs profilings of 10 year distant-relapse free survival and the controls. The differentially-expressed Micro RNAs were identified use GEO2 R tool. The upstream transcription factor( TF) and downstream target genes of differentially-expressed Micro RNAs were investigated with prediction websites. Function and pathway of target genes were annotated by DAVID. Regulating network of TF-mi RNA-target gene were constructed by cytoscape.Results A total of 5 miRNAs were differentially expressed( 3up-and 2 down-regulated). 5 upstream TFs and 154 downstream target genes were found respectively. Functional enrichment analysis indicated that negative regulation of BMP signaling pathway,cytoskeleton organization,signaling by TGF beta,signaling by Rho GTPases were involved. Conclusion hsa-miR-210,hsa-miR-33 a,hsa-miR-32,hsa-miR-13 a,hsa-miR-30a-3p were the differentially-expressed mi RNAs relevant to prognosis of breast cancer. Our study systemically characterize mi RNAs expression changes using bioinformatics methods to the benefit of the diagnosis and treatment for breast caner prognosis.更多还原