弥漫大B细胞淋巴瘤微小RNA的异常表达及核心基因筛选

Identification of differentially expressed microRNA and hub gene in diffuse large B-cell lymphoma

目的:寻找弥漫大B细胞淋巴瘤(DLBCL)中异常表达的微小RNA(miRNA)及其核心基因(hub基因),以期为DLBCL的发病机制研究提供新的靶标。方法:从GEO数据库中选择GSE117063数据集,该数据集包括17例DLBCL患者和14例健康对照的血浆样本,借助GEO2R工具筛选差异表达的miRNA,之后在miRTarBase网站预测miRNA的靶基因,使用DAVID网站对靶基因进行GO基因功能和KEGG通路富集分析。此外,通过蛋白质相互作用(PPI)网络筛选hub基因,构建miRNA-hub基因调控网络。最后,采用GEPIA数据库验证hub基因在DLBCL和正常组织中的表达。结果:与健康对照相比,hsa-miRNA-326在DLBCL样本中表达上调,hsa-miRNA-375表达下调,其调控的靶基因主要富集在HTLV-I感染通路和PI3K/AKT信号通路及基质中的蛋白多糖等通路,7个hub基因(AKT1、CCND1、ERBB2、TP53、MYC、CTNNB1和HSP90AA1)经验证在DLBCL中存在异常表达。结论:miRNA-326和miRNA-375及其靶基因可能在DLBCL的发病机制中发挥重要作用。

OBJECTIVE:To identify differentially expressed microRNA(miRNA)and hub gene associated with diffuse large B-cell lymphoma(DLBCL)and to find novel targets for mechanistic studies of DLBCL.METHODS:Dataset GSE117063 was chosen from the Gene Expression Omnibus(GEO)database,which included plasma samples from 17 DLBCL patients and 14 healthy individuals,and DE-miRNAs were selected by GEO2R.The potential target genes were predicted by miRTarBase.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were implemented using Database for Annotation,Visualization and Integrated Discovery(DAVID).Additionally,hub genes were screened by the Protein-Protein Interaction(PPI)network and miRNA-gene regulatory network was constructed.Finally,differential expressions of hub genes were verified by Gene Expression Profiling Interactive Analysis(GEPIA).RESULTS:The up-regulation of hsa-miRNA-326 and down-regulation of hsa-miRNA-375 were significantly and differentially expressed in DLBCL and healthy tissues.The target genes mainly participated in positive regulation of cell proliferation and enriched in HTLV-I infection,PI3K-Akt signaling pathway,proteoglycans in cancer and so on.Seven regulated hub genes(AKT1,CCND1,ERBB2,TP53,MYC,CTNNB1 and HSP90AA1)were verified to be differentially expressed in DLBCL.CONCLUSION:The up-regulated miRNA-326 and down-regulaed miRNA-375 and target genes might play important roles in pathogenesis of DLBCL.