Fig. 6

The circNOX4/FAP axis establishes an inflammatory fibroblast niche to promote NSCLC progression via the secretion of IL-6. A Cytokine antibody array for the supernatants of sh-NC and sh-circNOX4 CAFs, arrows indicate the cytokines with significant changes. B Bubble diagram of KEGG pathway analysis between sh-NC CAFs and sh-circNOX4 CAFs showed the enriched pathways. C The secretion level of IL-6, CCL2, TGF-β2, and IGFBP-4 in CAFs transfected with sh-NC or sh-circNOX4. D Schematic illustration of the coculture system of CAFs and cancer cells. E The secretion level of IL-6 in the indicated coculture system of CAFs and A549. Con, control. F The secretion level of IL-6 in the indicated coculture system of CAFs and PC9. Con, control. G Spearman’s correlation between FAP and IL-6 in the LUAD and LUSC cohorts from the TCGA database. H GSEA of affected signatures in NSCLC from the TCGA database (FAP high vs. FAP low). I The effect of the circNOX4/FAP axis on the secretion level of IL-6. J The treatment with neutralizing IL-6 antibody partly reversed the effects of circNOX4 overexpression on the CAF-mediated migration ability of NSCLC cells. K The treatment with neutralizing IL-6 antibody partly reversed the effects of circNOX4 overexpression on the CAF-mediated invasion ability of NSCLC cells; while the addition of rhIL-6 partly reversed the effects of circNOX4 knockdown on the CAF-mediated invasion ability of NSCLC cells. **P < 0.01, ***P < 0.001