Construction of a circRNA-miRNA-mRNA network based on differentially co-expressed circular RNA in gastric cancer tissue and plasma by bioinformatics analysis

Abstract

Background: Increasing evidence implicates circular RNAs (circRNAs) have been involved in human cancer progression. However, the mechanism remains unclear. In this study, we identified novel circRNAs related to gastric cancer and constructed a circRNA-miRNA-mRNA network.Methods: Microarray dataset GSE83521 and GSE93541 were obtained from Gene Expression Omnibus (GEO). Then, we used computational biology to select differentially co-expressed circRNAs in GC tissue and plasma and detected the expression of selected circRNAs in gastric cell lines by quantitative real‑time polymerase chain reaction (qRT‑PCR). We also chose the candidate miRNAs and their target genes for circRNAs through online tools. Combining the predictions of miRNAs and target mRNAs, a competing endogenous RNA regulatory network was established. Functional and pathway enrichment analyses were performed, and interactions between proteins were predicted by using String and Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to elucidate the possible functions of these differentially expressed circRNAs.Results: The regulatory network constructed using the microarray datasets (GSE83521 and GSE93541) contained three differentially co-expressed circRNAs (DECs). A circRNA-miRNA-mRNA network was constructed based on 3 circRNAs, 43 miRNAs and 119 mRNAs. GO and KEGG analysis showed that regulation of apoptotic signaling pathway and PI3K−Akt signaling pathway were highest degrees of enrichment respectively. We established a protein-protein interaction (PPI) network consisting of 165 nodes and 170 edges and identified hub genes by MCODE plugin in Cytoscape. Furthermore, a core circRNA-miRNA-mRNA network was constructed base on hub genes. Hsa_circ_0001013 was finally determined to play an important role in the pathogenesis of GC according to the core circRNA-miRNA-mRNA network.Conclusions: We propose a new circRNA-miRNA-mRNA network associated with the pathogenesis of GC. The network may become a new molecular biomarker and be used to develop potential therapeutic strategies for gastric cancer.