结直肠癌miRNA相关的Ascl2靶基因中的预后标志物

Prognostic markers of miRNA-related Ascl2 target genes in colorectal cancer patients

目的探讨结直肠癌细胞中miRNA相关的Ascl2靶基因对结直肠癌患者的临床预后价值。方法分析GEO数据库中干扰结肠癌LS174T细胞Ascl2表达的miRNA芯片数据(GSE34926)和基因RNA-Seq数据进行差异基因表达分析(GSE69036),通过对miRNA靶基因预测和差异基因表达对比,获得miRNA相关的Ascl2靶基因DEGs并行GO和KEGG分析,通过蛋白质互作网络图而筛选关键基因。用Kaplan-Meier方法进行生存分析。结果干扰Ascl2的LS174T细胞内存在符合条件的350个miRNA及其4640靶基因(DEG1);干扰Ascl2的LS174T细胞内出现1582个差异表达基因(DEG2);交集的534个基因定义为miRNA相关的Ascl2靶基因;GO分析这些基因富集在蛋白结合和转录抑制,KEGG分析这些基因集中在代谢相关通路和癌症相关的miRNA等通路;PPI网络得到43个关键基因,其中4个关键基因COPS3、DYNLL2、RAB6A与COPG1与结直肠癌患者的生存有相关性,并且未见文献报道。结论结直肠癌细胞Ascl2可通过miRNA调控具有不同的生物学功能的靶基因,其中COPS3、DYNLL2、RAB6A与COPG1可成为预测结直肠癌患者预后的新标志物。

Objective To explore the prognostic value of miRNA-related Ascl2 target genes in colorectal cancer(CRC) patients.Methods The data of microRNA microarray(GSE34926) and gene RNA-Seq(GSE69036) interfering with the expression of Ascl2 in colon cancer LS174 T cells in GEO database were analyzed for differential gene expression analysis.Through the prediction of miRNA target genes and the comparison of differential gene expression,the miRNA-related target genes namely differentially expressed genes(DEGs) were obtained and analyzed through gene ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.The hub genes were screened by the protein-protein interaction(PPI) network.The Kaplan-Meier method was used for survival analysis.Results There were 350 miRNAs and 4640 target genes(DEG1) in the LS174 T cells that interfered with Ascl2,1582 differentially expressed genes(DEG2) in the LS174 T cells that interfered with Ascl2,and 534 genes simultaneously in both DEG1 and DEG2 were defined as miRNA-related Ascl2 target genes.GO analysis showed that these genes were enriched in protein binding and transcriptional inhibition,KEGG analysis showed that these genes were mainly involved in metabolism related pathways and cancer-related miRNA pathways.A total of 43 hub genes were obtained in the PPI network,among which four hub genes COPS3,DYNLL2,RAB6 A and COPG1 were associated with the survival of colorectal cancer patients,and have not been reported in literature.Conclusion In colorectal cancer cells,Ascl2 can regulate target genes with different biological functions through miRNA,among which COPS3,DYNLL2,RAB6 A and COPG1 can be potential new prognostic markers for CRC patients.