Gastric cancer (GC) is the most common malignancy of the stomach. This study was aimed at elucidating the regulatory network of circRNA-miRNA-mRNA and identifying the precise inflammation-related targets in GC. The expression profiles of GSE83521, GSE78091, and GSE33651 were obtained from the GEO database. Interactions between miRNAs and circRNAs were investigated by the Circular RNA Interactome, and targets of miRNAs were predicted with miRTarBase. Then, a circRNA/miRNA/mRNA regulatory network was constructed. Also, functional enrichment analysis of selected differentially expressed genes (DEGs) was performed. The inflammation-/GC-related targets were collected in the GeneCards and GenLiP3 database, respectively. And a protein-protein interaction (PPI) network of DE mRNAs was constructed with STRING and Cytoscape to identify hub genes. The genetic alterations, neighboring gene networks, expression levels, and the poor prognosis of hub genes were investigated in cBioPortal, Oncomine, and Human Protein Atlas databases and Kaplan-Meier plotter, respectively. A total of 10 DE miRNAs and 33 DEGs were identified. The regulatory network contained 26 circRNAs, 10 miRNAs, and 1459 mRNAs. Functional enrichment analysis revealed that the selected 33 DEGs were involved in negative regulation of fat cell differentiation, response to wounding, extracellular matrix- (ECM-) receptor interaction, and regulation of cell growth pathways. THBS1, FN1, CALM1, COL4A1, CTGF, and IGFBP5 were selected as inflammation-related hub genes of GC in the PPI network. The genetic alterations in these hub genes were related to amplification and missense mutations. Furthermore, the genes RYR2, ERBB2, PI3KCA, and HELZ2 were connected to hub genes in this study. The hub gene levels in clinical specimens were markedly upregulated in GC tissues and correlated with poor overall survival (OS). Our results suggest that THBS1, FN1, CALM1, COL4A1, CTGF, and IGFBP5 were associated with the pathogenesis of gastric carcinogenesis and may serve as biomarkers and inflammation-related targets for GC.

中文翻译：

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全面分析circRNA-miRNA-mRNA网络以揭示潜在的与胃腺癌炎症相关的靶标。

胃癌（GC）是最常见的胃恶性肿瘤。这项研究旨在阐明circRNA-miRNA-mRNA的调控网络，并确定GC中与炎症相关的确切靶标。GSE83521，GSE78091和GSE33651的表达谱是从GEO数据库获得的。通过环形RNA相互作用组研究了miRNA和circRNA之间的相互作用，并使用miRTarBase预测了miRNA的靶标。然后，构建了一个circRNA / miRNA / mRNA调控网络。同样，对选定的差异表达基因（DEG）进行了功能富集分析。炎症/ GC相关靶标分别收集在GeneCards和GenLiP3数据库中。并用STRING和Cytoscape构建了DE mRNA的蛋白-蛋白相互作用（PPI）网络，以鉴定轮毂基因。分别在cBioPortal，Oncomine和Human Protein Atlas数据库和Kaplan-Meier绘图仪中研究了轮毂基因的遗传改变，邻近基因网络，表达水平和不良预后。总共鉴定出10个DE miRNA和33个DEG。调控网络包含26个circRNA，10个miRNA和1459个mRNA。功能富集分析表明，所选的33个DEG参与了脂肪细胞分化的负调控，对伤口的反应，细胞外基质（ECM-）受体相互作用以及细胞生长途径的调控。在PPI网络中，选择THBS1，FN1，CALM1，COL4A1，CTGF和IGFBP5作为GC的炎症相关中枢基因。这些中枢基因的遗传改变与扩增和错义突变有关。此外，基因RYR2，ERBB2，PI3KCA，这项研究将HELZ2和HELZ2与中枢基因相连。在GC组织中，临床标本中的枢纽基因水平显着上调，并且与较差的总体生存率（OS）相关。我们的结果表明，THBS1，FN1，CALM1，COL4A1，CTGF和IGFBP5与胃癌的发病机理有关，并且可能是GC的生物标志物和炎症相关靶标。