葡萄膜黑色素瘤生存预后相关lncRNA的初步筛选及相关性分析

Preliminary Screening and Analysis of Survival Prognostic lncRNA in Uveal Melanoma

目的:通过构建lncRNA-miRNA-mRNA的内源竞争RNA(ceRNA)网络,筛选与葡萄膜黑色素瘤(UM)生存预后相关的长链非编码RNA(lncRNA),并进行相关性分析。方法:以生物信息学为手段,通过疾病预后相关分析,LncRNA亚细胞定位检索,从肿瘤基因组图谱数据库中筛选lncRNA表达数据集。通过mircode数据库和targetscan数据库找到lncRNAs对应的靶microRNA(miRNA),Venn分析筛选出共同的与UM预后相关的miRNA。在多个数据库中同时检索,筛选出共同的miRNA-mRNA。通过KEGG富集与lncRNA-miRNA-mRNA网络可视化,最终确定出与UM生存预后相关的候选lncRNA。结果:在对lncRNA的下游靶miRNA及功能基因的预测中,鉴定出了630对候选miRNA-mRNA。通过ceRNA调控基因表达的机制,筛选出了9个可能发挥ceRNA功能的lncRNA。KEGG分析得到lncRNA的下游调控基因主要富集在参与肿瘤病理进程的信号通路中。SHNG6可能通过调控has-miR-214-5p、has-miR-214-3p、has-miR-let-7b-5p、has-miR-let-7c-3p等miRNAs,调节下游的功能基因BAX、IGF1R、KRAS、PIK3R1、PDGFD等。结论:lncRNAs通过ceRNAs机制,调控一系列参与肿瘤发生发展的致癌基因的表达,影响UM的预后及治疗,SHNG6、LINC01278等lncRNAs可能在其发生发展、迁移及侵袭等方面扮演着重要角色。

Objective:To construct a competing endogenous RNA(ceRNA)network of lncRNA-miRNA-mRNA,and to screen the long non-coding RNA(lncRNA)associated with the survival prognosis of uveal melanoma(UM).Methods:In this study,the expression data set of lncRNA was screened from the Tumor Genome Atlas Database through disease prognosis correlation analysis and a subcellular localization search of lncRNA using bioinformatics methods.Target microRNAs(miRNAs)corresponding to lncRNAs were found by the mircode database,targetscan database,and common miRNAs associated with UM prognosis were screened out by Venn analysis.The common miRNA-mRNA was screened from multiple databases simultaneously.Through KEGG enrichment and lncRNA-miRNA-mRNA network visualization,candidate lncRNAs related to the survival prognosis of UM were finally identified.Results:In the prediction of downstream target miRNAs and the functional genes of lncRNAs,630 pairs of candidate miRNA-mRNA were identified.Based on the mechanism of gene expression regulation by ceRNAs,9 lncRNAs that might play the role of ceRNAs were screened out.KEGG analysis showed that the downstream regulatory genes of lncRNAs were mainly enriched in the signaling pathways involved in the pathological process of tumors.SHNG6 may regulate miRNAs such as has-miR-214-5p,has-miR-214-3p,has-miR-let-7b-5p,and has-miR-let-7c-3p,the regulators of downstream functional genes BAX,IGF1R,KRAS,PIK3R1,PDGFD and so on.Conclusions:Through the mechanism of ceRNAs,lncRNAs regulate the expression of a series of oncogenes involved in tumor genesis and development,and affect the prognosis and treatment of UM.lncRNAs such as SHNG6 and LINC01278 may play an important role in its occurrence,development,migration and invasion.