Reconstruction of miRNA-mRNA bipartite network in saliva of gastric cancer patients via bioinformatics analysis

Abstract Gastric cancer (GC) is the third leading cause of mortality worldwide (۱). microRNAs (miRNAs) have substantial roles in the GC progression (۲). miRNAs have attracted considerable research interest due to their potential applications as theranostic biomarkers. (۳). In this study, the miRNA-mRNA regulatory network was uncovered among saliva proliferating GC patients using bioinformatics analyses. The gene expression profiles (GSE۶۴۹۵۱) were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were analyzed using GEO۲R tools in two groups including ۳۱ healthy individuals and ۶۳ GC patients. Then, a defined formula [-log(p.value) × | log (fold change) | ] was applied to select the ۲۰۰۰-top significant probs. We established a protein-protein interaction (PPI) network of the DEGs through the (STRING) database and used Gephi software to select hub genes with a crucial role. Next, we employed the Toppgene database for Gene Ontology (GO). The Toppgene online database was also applied to select target miRNAs related to ۲۰ hub genes and reconstructed miRNA-mRNA regulatory network by Cytoscape software. In total, ۱۵۹۰ DEGs were identified. Additionally, ۱۰ hub genes (HSP۹۰AA۱, HSPA۴, ESR۱, JUN, CDK۱, ATM, CD۴۴, EZH۲, POLR۲A and CREB۱) with the highest degree were determined. The most frequent top ۲ GO of molecular function included cadherin binding and RNA binding; of biological process included regulation of RNA splicing and peptidyl-serine phosphorylation; and of cellular pathway included RHO GTPase Cycle and Hippo Signaling. The network five hub (highest degrees of association) mRNAs (SMAD۲, ESR۱, CREB۱, CD۴۴, and CXCL۸) and miRNAs (miR-۲۶a, miR-۶۵۶, miR-۶۰۷, miR-۲۰۳a, and miR-۳۰۲b) were determined. We reconstructed a salivary miRNA-mRNA bipartite network with potential functions in the saliva of GC patients, demonstrating their potential theranostic applications as biomarkers.

کلیدواژه ها:

biomarkers ، miRNA ، gastric cancer