弱精子症相关microRNAs和基因的生物信息学研究

Bioinformatics of microRNAs and genes associated with asthenospermia

目的:基于生物信息学方法探讨弱精子症相关的microRNAs(miRNAs)和基因,为弱精子症的诊疗提供新的思路。方法:通过pubmed和web of science筛选文献确定与弱精子症相关的miRNAs,然后通过TargetScan数据库预测其靶基因。在基因表达综合数据库(GEO)中选择与弱精子症相关的数据集GSE92578,通过GEO_(2)R软件分析获取差异表达基因(DEGs)。对上述miRNAs的靶基因和分析获得的DEGs取交集,获取最终的DEGs。利用DAVID数据库对上述DEGs进行基因本体分析(GO)和京都基因与基因组百科全书(KEGG)信号通路富集分析。然后,基因STRING数据库进行蛋白互作(PPI)网络分析获得关键基因,再通过cytoscape软件及其插件cytoHubba获取节点基因。结果:通过文献共筛选出7个差异表达的miRNAs和84个差异表达基因。GO富集分析结果,差异基因参与的生物过程(BP)主要包括同源蛋白绑定,蛋白激酶绑定和蛋白质丝氨酸/苏氨酸激酶活动;细胞组成(CC)主要包括细胞质、细胞膜、溶酶体膜和顶体等;分子功能(MF)主要包括RNA聚合酶Ⅱ启动子的转录进行正向调节、蛋白质转移、细胞外基质组织和磷酸化作用的正向调节等。KEGG相关通路涉及PI3K-Akt信号通路、人类乳头瘤病毒感染通路、血小板激活和化学致癌-受体激活等通路。并通过cytoscape获得10个节点基因分别为AKT1、MAPK3、BRD4、DNMT3A、FURIN、LMNB2、COL5A2、COL5A3、COL11A1、COL27A1。结论:本研究获得的miRNAs、hub基因和相关通路,在弱精子症病理程中可能发挥着重要的作用,可为后续机制研究提供参考靶点。

Objective:To explore the microRNAs(miRNAs)and genes associated with asthenospermia based on bioin-formatics methods,and to provide the new ideas for the diagnosis and treatment of asthenospermia.Methods:The miRNAs associated with asthenospermia were identified by screening the literatures in pubmed and Web of science,and then their target genes were predicted by TargetScan database.The data set GSE92578 related to asthenospermia selected from gene expression omnibus(GEO)and GEO_(2)R software was used to analyze for obtaining Differential Ex-pression Genes(DEGs).The target genes of the miRNAs and the DEGs from this analysis were intersected to obtain the final DEGs.The analysis of the gene ontology(GO)and the Kyoto encyclopedia and genomes(KEGG)genes sig-naling pathway enrichment of the DEGs were performed using the DAVID database.Then,the key genes were ob-tained by the analysis of the protein interaction(PI)network in Gene STRING database,and the node genes were ob-tained by cytoscape software and its plug in cytoHubba.Results:A total of 7 differentially expressed miRNAs and 84 differentially expressed genes were screened through the literature.The results of GO enrichment analysis showed that the biological processes(BP)involved by the differential genes were mainly included the homologous protein binding,the protein kinase binding and the protein serine/threonine kinase activities.The cellular components(CC)mainly in-cluded cytoplasm,cell membrane,lysosomal membrane,and acrosome,etc.The molecular functions(MF)mainly in-cluded the positive regulation of transcription from RNA polymerase II promoter,the positive regulation of protein translocation,extracellular matrix organization,and phosphorylation,etc.KEGG related pathways involved PI3K Akt signaling pathway,human papillomavirus infection pathway,platelet activation and chemoattenuation receptor activa-tion pathways.The 10 node genes obtained by cytoscape were AKT1,MAPK3,BRD4,DNMT3A,FURIN,LMNB2,.COL5A2,COL5A3,COL11A1 and COL27A1.Conclusion:The miRNAs,hub genes and the related pathways ob-tained in this study may play the important roles in the pathological process of the spermatogenesis of the patients,and which may provide the reference targets for the subsequent mechanistic studies on the spermatogenesis.