【摘要】 目的利用TCGA数据库探寻miRNA-519a在子宫内膜癌中的诊断及预后价值及机制。方法通过对TCGA数据库中UCEC数据进行差异表达和生存分析,挑选出肿瘤组织中显著高表达且高表达提示预后不良的miRNA,并对该miRNA的靶基因进行富集分析,将富集出的关键通路中的mRNA与UCEC组织中低表达的mRNA交集,找出miRNA在UCEC中的靶基因和通路,并进一步利用双荧光素酶报告基因分析检测miRNA与靶基因mRNA的靶向结合进而调控其功能。结果 TCGA-UCEC数据库中癌旁组织和癌组织存在不同miRNA差异表达,共148个miRNA上调,75个miRNA下调(|logFC|>2);进一步对差异表达miRNA进行预后分析发现,和正常组织相比,miRNA-519a在UCEC组织中显著高表达,且高表达的患者预后不良;通过mirDB数据库预测miRNA-519a靶基因(共685个),并用DAVID数据库将这些mRNA进行KEGG-PATHWAY富集分析,发现miRNA-519a的靶基因富集于肿瘤相关通路,且该通路相关基因中PDGFRA和TGFBR2在UCEC组织中显著低表达;双荧光素酶报告基因分析证明,miRNA-519a可与PDGFRA和TGFBR2 mRNA的3’-UTR直接结合并抑制两者的表达。结论 miRNA-519a能够作为UCEC诊断和预后的生物标志物,miRNA-519a通过调控PDGFRA和TGFBR2的表达进而调控肿瘤的进程。更多还原

【Abstract】 Objective To explore the diagnostic and prognostic value and mechanism of microRNA519 a in endometrial cancer based on TCGA database. Methods Through differential expression and survival analysis of UCEC data in TCGA database, we selected microRNAs with high expression and poor prognosis in tumor tissues, enriched and analyzed the target genes of microRNAs, and intersected the genes of key pathways with those of low expression in UCEC tissues to identify mi. The target genes and pathways of miRNA in UCEC. Luciferase reporter assays were used to detect binding of miRNA to the 3’-non-coding region(3’UTR) of the target gene m RNA. Results There were different microRNAs differentially expressed in adjacent tissues and cancer tissues in TCGA-UCEC database. A total of 148 microRNAs were up-regulated and 75 microRNAs were down-regulated(| logFC |> 2). Further prognostic analysis of differentially expressed microRNAs showed that miRNA-519 a was significantly higher in UCEC tissues than in normal tissues, and patients with high expression had poor prognosis. The target genes of miRNA-519 a(685 in total) were predicted by mirDB database. KEGG-PATHWAY enrichment analysis(Fig.3) was performed on these genes using DAVID database. It was found that the target genes of miRNA-519 a were most abundant in cancer-related pathways, and PDGFRA and TGFBR2 were significantly lower expressed in UCEC tissues. Furthermore, the luciferase reporter gene analysis demonstrated that miRNA-519 a could bind directly to 3’-UTR of PDGFRA and TGFBR2 and inhibit the mRNA expression. Conclusion miRNA-519 a could be a biomarker for diagnosis and prognosis of UCEC, miRNA-519 a regulates the progression of cancer by regulating PDGFRA and TGFBR2.更多还原