miR-139-5p靶基因参与调控人骨肉瘤细胞表型的机制分析

目的通过生物信息学方法预测miR-139-5p的靶基因,并对靶基因进行信号通路富集分析,结合蛋白质互作(PPI)网络分析筛选核心基因。方法使用dbDEMC数据库检索miR-139-5p在骨肉瘤细胞中的表达,使用miRSystem网站的生物信息学数据库进行miR-139-5p的靶基因预测,利用DAVID6.8软件对miR-139-5p的靶基因开展KEGG信号通路富集分析,利用string软件对KEGG聚类分析中发现的与肿瘤密切相关的基因进行PPI网络分析,获得相关参数,然后将数据导入Cytoscape 3.8软件,由其插件MCODE筛选出核心基因,并利用HCMDB数据库分析其在骨肉瘤中的表达,选择有阳性意义的基因作为核心基因。结果miR-139-5p表达水平在骨肉瘤细胞中明显下调(P<0.05)。预测分析共获得407个靶基因,富集在59条信号通路中,其中与肿瘤关系密切的通路有21条,分别是mTOR通路、癌症中的蛋白多糖、小细胞肺癌、cAMP信号通路、细胞外受体相互作用、焦点粘连、胶质瘤等。PPI网络分析显示,21条信号通路中的NOTCH1、FN1、CXCR4和RPS6KB1是参与miR-139-5p调控人骨肉瘤细胞生物表型的关键核心基因。结论miR-139-5p可能是骨肉瘤细胞中潜在的抑癌基因,与骨肉瘤具有相关性,富集于21条信号通路中的癌基因的异常表达与其细胞恶性表型具有显著相关性。靶基因NOTCH1、FN1、CXCR4和RPS6KB1是miR-139-5p调控骨肉瘤发生、发展及预后的关键核心基因。另外,生物信息学分析发现的具有高度相关性的癌基因和信号通路为探讨其功能和机制提供了线索和依据。

Mechanism analysis of miR-139-5 p targeted regulating core genes for participating in human osteosarcoma cell phenotype

Objective To predict the target genes of miR-139-5p by bioinformatics methods,and to screen the core genes by the signal pathway enrichment analysis and protein-protein interaction(PPI)network analysis on the targeted genes.Methods The expression of miR-139-5p in osteosarcoma cells was retrieved by using dbDEMC database,the bioinformatics database in the miRSystem network station was used to predict the target genes of miR-139-5p,the David6.8 software was used to carry out the KEGG signal pathway enrichment analysis,the string software was used to conduct the PPI network analysis on the genes closely related to tumor found in KEGG cluster analysis,the related parameters were obtained,then the data were imported into Cytoscape 3.8,the core genes were screened out by its plug-in MCODE,their expression in osteosarcoma were analyzed by using the HCMBD database.Finally,those genes with positive significance were selected as the core genes.Results The expression level of miR-139-5p was significantly down-regulated in osteosarcoma(P<0.05),a total of 407 target genes were obtained by predictive analysis,which were enriched in 59 signaling pathways,21 pathways were closely related to cancer,including mTOR pathway,proteoglycan in cancer,small cell lung cancer,cAMP signaling pathway,extracellular receptor interaction,focal adhesion,glioma,etc.The PPI network analysis showed that NOTCH1,FN1,CXCR4 and RPS6KB1 in 21 signal pathways were the key core genes involved in miR-139-5p regulating the biological phenotype of human osteosarcoma cells.Conclusion miR-139-5p may be a potential tumor suppressor gene in osteosarcoma cells,has the correlation with osteosarcoma,the cancer gene abnormal expression enriched in 21 signal pathways has the significant correlation with the malignant phenotype of osteosarcoma cells.The target genes NOTCH1,FN1,CXCR4 and RPS6KB1 are the key core genes of miR-139-5p in regulating the occurrence,development and prognosis of osteosarcoma cells.In addition,the oncogenes and signaling pathways with high correlation found by bioinformatical analysis provide clues and basis for exploring their functions and mechanisms.