Icariin Regulates the hsa_circ_0003159/eIF4A3/bcl-2 Axis to Promote Gastric Cancer Cell Apoptosis.

Abstract

Objective To clarify the mechanism of icariin (ICA) promoting gastric cancer (GC) cell apoptosis by regulating circ_0003159/eIF4A3/bcl-2 axis. Methods The mRNA or protein levels were detected by qRT-PCR or the western blot. The interaction between eIF4A3 protein and circ_0003159 or eIF4A3 protein and bcl-2 mRNA were validated by RNA pull down assays and the RNA immunoprecipitation (RIP) assay. The cell viability was measured by the cell counting kit (CCK)-8 kit. The cell apoptosis was measured by flow cytometry. Results Compared with the group Vector, the ratio of cytoplasmic eIF4A3/nuclear eIF4A3 in the cell with circ_0003159 overexpression was significantly higher. RIP and RNA pull down results proved the interaction between eIF4A3 and circ_0003159. The RIP assay further validated the interaction between eIF4A3 and bcl-2. By gain or loss of the functional experiment, hsa_circ_0003159 was proved to recruit eIF4A3 to inhibit bcl-2 expression. Hsa_circ_0003159 regulates eIF4A3/bcl-2 to reduce GC cell viability and increase apoptosis Furthermore, ICA regulates hsa_circ_0003159/eIF4A3/bcl-2 axis to inhibit GC cell activity and induce GC cell apoptosis in vitro. Conclusion These data showed that ICA could effectively reduce the GC cell activity and induce GC cell apoptosis via hsa_circ_0003159/eIF4A3/bcl-2 axis, which provides new theoretical evidence for the treatment of GC by ICA.