小核仁RNA宿主基因4在胃癌中的预后价值及潜在作用机制

Prognostic value and potential mechanism for the role of SNHG4 in gastric cancer

目的旨在探讨小核仁RNA宿主基因4(SNHG4)在胃癌组织中的表达、预后价值及可能作用机制。方法运用UALCAN数据库分析SNHG4在胃癌中的表达情况;Kaplan-Meier Plotter数据库分析SNHG4与胃癌预后的关系;StarBase、Targetscan、microT-CDS数据库及Cytoscape软件构建SNHG4-miRNA-mRNA调控网络;DAVID数据库对SNHG4相关miRNA的靶基因进行生物学功能及通路分析。结果SNHG4在胃癌组织中的表达明显高于正常组织(P=8.882E-16)。生存分析发现SNHG4高表达的胃癌患者总体生存时间少于低表达组(P=8.900E-05)。通过RNA调控网络的构建,发现在胃癌中hsa-let-7a-5p(P=1.02E-03)、hsa-miR-152-3p(P=4.51E-06)、hsa-miR-204-5p(P=6.68E-04)和hsa-miR-363-3p(P=8.06E-03)可作为SNHG4的结合位点。SNHG4作用于这4种miRNA进一步调控250个靶基因。对靶基因的GO注释及KEGG富集分析,发现这些靶基因在蛋白质磷酸化的调节、转录负调控、RNA聚合酶II启动子的转录等生物过程中发挥作用,且通过阻断或激活Wnt等信号通路参与胃癌的发生及发展。结论SNHG4可作为胃癌潜在的诊断性肿瘤标志物,判断胃癌预后情况,通过构建SNHG4-miRNA-mRNA调控网络,从分子水平研究胃癌的发病机制,为实验研究及临床研究提供明确方向。

Objective To investigate the expression,prognostic value and potential mechanism for the role of SNHG4 in gastric cancer.Methods The expression of SNHG4 in gastric cancer was analyzed by UALCAN database.The relationship between SNHG4 and prognosis of gastric cancer was analyzed by Kaplan-Meier Plotter.SNHG4-miRNA-mRNA regulatory network was constructed by StarBase,Targetscan,microT-CDS and Cytoscape.The target genes were analysis GO and KEGG pathway enrichment by DAVID database.Results The expression of SNHG4 in gastric cancer was significantly higher than that in normal tissues(P=8.882E-16).The overall survival time of patients with high SNHG4 expression was lower than that of patients with low expression(P=8.900E-05).Through the construction of RNA regulatory network,we found that hsa-let-7a-5p(P=1.02E-03),hsa-miR-152-3p(P=4.51E-06),hsa-miR-204-5p(P=6.68E-04)and hsa-miR-363-3p(P=8.06E-03)could be used as the binding sites of SNHG4 in gastric cancer,and these four miRNAs further regulated 250 downstream target genes.Through GO and KEGG enrichment analysis of the target genes,we found that these target genes played roles in the biological process of protein phosphorylation regulation,transcription negative regulation,RNA polymerase II promoter transcription,and participated in the occurrence and development of gastric cancer by blocking or activating Wnt and other signal pathways.Conclusions SNHG4 can be used as a potential tumor marker for gastric cancer to judge the prognosis of gastric cancer.By constructing a SNHG4-miRNA-mRNA regulatory network,the pathogenesis of gastric cancer can be studied at the molecular level.This provides a clear direction for experimental and clinical research.