前列腺癌组织中具有潜在生物标记物特性的miRNA及其靶基因生物学功能、信号通路分析

Biological function and signal pathway analysis of microRNA and its target genes with potential biomarker characteristics in prostate cancer tissues

目的筛选前列腺癌组织中具有潜在生物标记物特征的微小RNA(miRNA),并分析其靶基因的生物学功能及信号通路。方法采用癌症和肿瘤基因图谱计划(TCGA)数据库下载前列腺癌相关数据集,分析前列腺癌组织与癌旁组织miRNA的表达情况,筛选差异表达miRNA,采用Kaplan-Meier生存曲线分析前列腺癌患者的生存情况,筛选出具有潜在生物标记物特性(高表达、预后差)的miRNA。采用生物信息学在线网站预测有潜在生物标记物特性miRNA的靶基因,进行基因本体(GO)富集分析和基因组百科全书(KEGG)通路富集分析,分析有潜在生物标记物特性miRNA的靶基因主要参与的生物学功能及肿瘤相关通路。结果前列腺癌组织、癌旁组织共159个差异表达miRNA,其中表达下调59个、表达上调100个。生存分析结果显示,miR-17高表达的胰腺癌患者预后差。前列腺癌组织、癌旁组织miR-17的相对表达量分别为3 852. 66±1 800. 41、1 581. 22±391. 71,二者比较,P <0. 001。miR-17共138个靶基因,主要参与转录DNA模版化、蛋白质磷酸化、甲基胞嘧啶分解代谢、正调控凋亡过程、钠离子跨膜转运、胞质分裂等生物学过程;主要分子功能包括它们与蛋白激酶结合、核酸结合、金属离子结合、钙离子结合、蛋白质结合等。与miR-17靶基因有关的信号通路有雌激素信号通路、c AMP信号传导途径、趋化因子信号通路、HIF-1信号通路和癌症蛋白聚糖信号通路等13条信号通路。结论 miR-17可作为前列腺癌发生和预后评价的潜在生物标记物。

ObjectiveTo screen the microRNA(miRNA)with potential biomarker characteristics in prostate cancer tissues,and to analyze the biological functions and signal pathways of its target genes.Methods From cancer and cancer genome program(TCGA)database,we downloaded the prostate cancer dataset,and analyzed the expression of miRNA in the prostate tissues and the adjacent carcinoma tissues,and screened out the differentially expressed miRNAs;Kaplan-Meier survival curves were used to analyze the survival of patients with prostate cancer,and miRNAs with potential biomarker characteristics(high expression and poor prognosis)were screened out.Target genes with potential biomarker characteristics were predicted by bioinformatics online website,and gene ontology(GO)enrichment analysis and Kyoto gene and genome encyclopedia(KEGG)pathway enrichment analysis were conducted to analyze the biological functions and tumor-related pathways of target genes with potential biomarker characteristics.Results A total of 159 differentially expressed miRNAs were found in the prostate cancer tissues and adjacent tissues,among which,59 were down-regulated and 100 were up-regulated.Survival analysis revealed poor prognosis in pancreatic cancer patients with high miR-17 expression.The relative expression levels of miR-17 in the prostate cancer tissues and adjacent tissues were 3 852.66±1800.41 and 1 581.22±391.71,respectively.The miR-17 had a total of 138 target genes,which were mainly involved in the biological processes such as transcriptional DNA template,protein phosphorylation,methylcytosine catabolism,positive regulation of apoptosis,transmembrane transport of sodium ions,and cytokinesis;the main molecular functions included their binding to protein kinase,nucleic acid,metal ion,calcium ion and protein.The signaling pathways related to miR-17 target genes included 13 estrogen signaling pathway,such as cAMP signaling pathway,chemokine signaling pathway,HIF-1 signaling pathway and cancer proteoglycan signaling pathway,and so on.Conclusions The miR-17 can be used as a potential biomarker for the occurrence and prognosis of prostate cancer.