血管肉瘤相关miRNAs的生物信息学预测及分析

Bioinformatics prediction and analysis of miRNAs associated with angiosarcoma

目的探讨血管肉瘤相关miRNAs及其靶基因在其恶性生物学行为中的作用。方法从GEO数据库中下载血管肉瘤miRNAs表达谱芯片数据,应用GEO2R筛选出差异表达的miRNAs并进行靶基因预测,对靶基因进行GO及KEGG生物功能富集分析及蛋白互作分析。结果筛选出53个差异表达的miRNAs(P<0.05,|log fold-change|≥4),其中上调者51个,下调者2个;GO功能富集分析发现差异表达miRNAs的靶基因主要参与细胞通讯、信号转导等生物学过程;KEGG信号通路富集分析发现靶基因主要参与肿瘤信号通路、代谢通路、环腺苷酸(cAMP)信号通路、丝裂原活化蛋白激酶(MAPK)信号通路、PI3K/AKT信号通路、Ras信号通路等重要通路;String蛋白互作分析发现,STAT3、TP53、MAPK1、SRC等在蛋白互作网络中处于核心地位。结论异常表达的miRNAs在血管肉瘤的恶性生物学行为中发挥着关键作用,为进一步探讨血管肉瘤发生、发展的具体分子机制、分子标志物的筛选及靶向药物的开发奠定基础。

Purpose To explore the role of miRNAs associated with angiosarcoma and their target genes in malignant biological behaviors of angiosarcoma.Methods The microarray dataset of miRNAs expression of angiosarcoma was downloaded from Gene Expression Omnibus(GEO)database,and differentially expressed miRNAs were obtained by GEO2R,then potential target genes were predicted,Gene Oncology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses of the target genes were performed.The protein-protein interaction network construction was obtained from String.Results A total of 53 differentially expressed miRNAs were identified between angiosarcoma tissue and capillary hemangioma tissue according to P<0.05,|log fold-change|≥4,of which 51 miRNAs were up-regulated and 2 miRNAs were down-regulated.GO function enrichment analysis showed that target genes of differentially expressed miRNAs mainly involved in biological processes of cell communication,signal transduction.Pathway enrichment analysis found that target genes were mostly enriched in pathways in cancer,metabolic pathways,cAMP signaling pathway,MAPK signaling pathway,PI3K/AKT signaling pathway,Ras signaling pathway.String protein interaction analysis found that STAT3,TP53,MAPK1,SRC,etc.Might be the key proteins contributed to tumorigenesis or tumor progression in angiosarcoma.Conclusion Abnormally expressed miRNAs play a key role in the malignant biological behavior of angiosarcoma,which lays the foundation for further study of the specific molecular mechanisms,the screening of molecular markers and developing targeted therapy for angiosarcoma.