Fig 1: SLC25A22 knockout abrogates secretion of CXCL1 and CXCL3 in vitro and in vivo.a RNA-seq of SLC25A22 knockout DLD1 cells and gene set enrichment analysis (GSEA) for the identification of common differentially regulated pathways in SLC-KO1 and SLC-KO2 cells (n = 4). b, c GSEA enrichment scores for differentially regulated gene sets unveiled the cytokine-cytokine receptor interaction signaling pathway as the top pathway depleted in SLC25A22 knockout cells. d Inflammatory Response and Autoimmunity PCR array showed that CXCL1, CXCL3 and IL1B were induced in ApcMin/+KrasG12D/+Villin-Cre mice tumors, but were down-regulated by SLC25A22 knockout (FC > 2). e qPCR validated that SLC25A22 knockout inhibited CXCL1/3 mRNA in DLD1, CT26 and Colo26 cells (n = 3). Each dot represents an independent sample. f Antibody array showed SLC25A22 knockout down-regulated cytokine secretion in DLD1 cells. g Densitometry showed CXCL1 and CXCL1/2/3 were top-down-regulated cytokines. h ELISA confirmed SLC25A22 knockout impaired CXCL1/3 secretion in DLD1 (72 h), CT26 (24 h) and Colo26 (24 h) (n = 3). Each dot represents an independent sample. i Detection of CXCL1/3 in serum and tumors of mice implanted with CT26 allografts (left, n = 5) and ApcMin/+KrasG12D/+ organoid allografts (right, n = 10) with or without SLC25A22. Each dot represents an independent mouse. j SLC25A22 mRNA correlates with CXCL1/2/3 mRNA in TCGA CRC (COADREAD) cohort (n = 677). Each dot represents an independent patient. Data are shown as mean ± SD (e, h, i). Two-tailed one-way ANOVA (e, h, i). Two-tailed Student’s t test analysis for two-group comparison i. Pearson correlation test j. Source data are provided as a Source Data file.