Circular RNA hsa_circ_0094976 modulates GPR155 to inhibit gastric adenocarcinoma malignant characteristics by targeting miR-223-3p.

Background: The abnormal expression of circular RNA (circRNA) has been confirmed to be closely related to the development of many human diseases including gastric adenocarcinoma (GA). This study aimed to elucidate the molecular mechanism and biological function of hsa_circ_0094976 (circ_0094976) in GA.

Methods: The expression of circ_0094976, miR-223-3p, and G protein-coupled receptor 155 (GPR155) mRNA was measured by quantitative real-time polymerase chain reaction. Cell viability, cell proliferation, colony formation, migration, and invasion were estimated by cell counting kit-8 assay, 5-Ethynyl-2'-deoxyuridine assay, colony formation assay, and transwell assay, respectively. The bioinformatics analysis, dual-luciferase reporter assay, and RNA pull-down assay were used for predicting and verifying the interaction of the circ_0094976/miR-223-3p/GPR155 axis. A xenograft mouse model was performed in nude mice to reveal the role of circ_0094976 in vivo.

Results: Circ_0094976 was down-regulated in GA tissues and GA cell lines compared to normal controls. Overexpression of circ_0094976 inhibited the GA cell growth, migration, and invasion in vitro, and tumor growth in vivo. Circ_0094976 directly targeted miR-223-3p, and GPR155 was a direct target of miR-223-3p. Moreover, circ_0094976 sponging miR-223-3p to increase the expression of GPR155.

Conclusion: We disclosed that circ_0094976 could act as a sponge of miR-223-3p to regulate the expression of GPR155, and further restrain the development of GA, which may provide new insight into the therapy of GA.