This study aimed to clarify the expression and role of hsa_circ_0003159 in gastric carcinogenesis, and validate the protective effects of Icariin (ICA) against gastric cancer (GC) cell growth through the in vitro and in vivo experiments. The levels of hsa_circ_0003159, microRNA (miR)-223-3p and NLRP3 were measured by Quantitative real time Polymerase Chain Reaction or western blot. The cell counting kit (CCK)-8 was used to determine cell proliferation. The target relationship of miR-223-3p/hsa_circ_0003159 and miR-223-3p/NLRP3 was predicted by bioinformatics and validated by the dual-luciferase reporter and pull-down assays. Xenograft model was constructed to assess the roles of hsa_circ_0003159 and protective effects of ICA in GC in vivo. Results showed that hsa_circ_0003159 was downregulated in GC cell lines and its overexpression promoted GC cell viability. MiR-223-3p was identified as a target of hsa_circ_0003159. By competitively sponging miR-223-3p, hsa_circ_0003159 positively regulated NLRP3 expression. MiR-223-3p mimics reversed the suppressive effect of hsa_circ_0003159 on GC cell viability and cell pyroptosis. Importantly, ICA inhibited GC cell viability and triggered GC cell pyroptosis by regulating the hsa_circ_0003159/miR-223-3p/NLRP3 axis in vitro and in vivo. In conclusion, this study indicated ICA inhibits GC cell growth by regulating the hsa_circ_0003159/miR-223-3p/NLRP3 signaling axis. This study not only reveals the mechanism of gastric carcinogenesis but also provides potential molecular targets and therapeutic tools for its treatment.
Keywords: Icariin; gastric cancer; hsa_circ_0003159/miR-223-3p/NLRP3 signaling axis.