Based on these findings, we summarized the TRAF6/IRF3 axis model regulating 5-FU-resistant GC cells (Fig. 7H): TRAF6 induces Lys70 ubiquitination of IRF3 by binding to IRF3-Δ (SR + IAD) (1-190aa), promotes the degradation of IRF3 protein, increases the NF-κB-p65 nuclear translocation, and ultimately promotes the proliferation and tumorigenesis of 5-FU-resistant GC cells. Here, NFKB1 is linked to gastric cancer.