Targeting IRF3 inhibits GC growth. (A) Cell proliferation of HGC27, BGC-823, and MKN45 cells after transfection with IRF3 siRNAs. (B) Colony formation of IRF3-depleted cells. (C) Cell proliferation of HGC27 and BGC-823 cells after transfection with IRF3 siRNAs (a mixture of two siRNAs) together with YAP(S127A). (D) Colony formation of IRF3-depleted cells after transfection with YAP(S127A). (E) Knockdown of endogenous IRF3 inhibited xenograft tumor growth. Mice were photographed after being killed. BALB/cA nu/nu mice (aged 4 wk) were injected with the GC cell lines (HGC-27, BGC-823, and MKN-45). Once palpable tumors were detected, pairs of mice were randomized and treated with lentivirus-delivered shIRF3 or scramble shRNA by subcutaneous injection (n = 10). (F) Tumor volumes for the mice from E. (G) Tumor numbers in WT and IRF3^−/− mice after administration of H. pylori intragastrically with alkylating agent MNNG in drinking water. 4-wk-old IRF3^−/− mice and their WT littermates were orally gavaged with 50 µl of bacterial suspension (∼10⁶ CFU) every day, which persisted for at least 6 mo before sacrifice. 100 mg/ml MNNG was added to the drinking water for a period of up to 2 mo. A total of 40 mice were reared, including 20 normal controls. (H) Ki67 staining of adenomas from G. Bar, 50 µm. (I) Relative mRNA levels of YAP target genes in gastric tissue from G. (J) Tumor numbers in WT and IRF3^−/− mice after administration of YAP lentivirus intragastrically with alkylating agent MNNG in drinking water. (K) Ki67 staining of adenomas from J. Bar, 50 µm. (L) Relative mRNA levels of YAP target genes in gastric tissue from J. At least two independent experiments were performed for all data. For curve figures and bar figures, data are presented as means ± SD. Unpaired Student’s t tests were used for comparing two variables. One-way ANOVA was used for multiple variables comparison. *, P < 0.05; **, P < 0.01; ***, P < 0.001; n.s., no significance in comparison with control group.