Identification and Characterization of the Roles of CircCASP9 in Gastric Cancer Based on a CircRNA–miRNA–mRNA Regulatory Network

Abstract

Background: Circular RNAs (circRNAs) play crucial roles in gastric cancer (GC). This study aimed to construct a new circRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network for GC and validate a specific circRNA in GC tissues and cell lines.Methods: We obtained circRNA profiles from an in-house circRNA microarray and the Gene Expression Omnibus (GEO) database, and microRNA (miRNA) profiles from StarBase and CircBank. Messenger RNA profiles were downloaded from GEO. We then constructed a ceRNA network using the extracted circRNA (circCASP9), miRNA (miR-589-5p) and 52 mRNAs. The expression of circCASP9 was confirmed in GC tissues and cell lines, using quantitative reverse transcription polymerase chain reaction. The function of circCASP9 was validated in GC cell lines, using the cell counting kit-8, ethynyl deoxyuridine, transwell, and colon assays. The sponge function of circCASP9 for miR-589-5p was verified using dual luciferase assays. Results: A novel ceRNA network was established with one downregulated circRNA, one upregulated miRNA, and 52 downregulated mRNAs. CircularCASP9 was downregulated in GC tissues and cell lines and sponged miR-589-5p. Furthermore, circCASP9 inhibited GC proliferation, migration, and invasion. Conclusions: We identified the expression and anticancer effects of the core circRNA circCASP9 in a novel circRNA-miRNA-mRNA ceRNA regulatory network of GC. This present study may provide a novel therapeutic target and insight understanding of the mechanism of gastric cancer.