Fig. 2: Dusp18 inhibition decreases cholesterol biosynthesis.

a Scheme for the AOM/DSS-induced colon cancer model in WT and CKO mice. b Colon tumor numbers in mice from (a), n = 6. c Survival curves, n = 10. d Representative IF images and quantification of CD8⁺ T cells in AOM/DSS-induced colon cancer formed by WT and CKO mice. Scale bar, 10 μm. For each mouse, five fields from one independent tumor of each mouse were analyzed (n = 6). GO (e) and KEGG (f) analyses show the altered pathways after Dusp18 inhibition. g Heatmap of RNA-seq expression values of cholesterol biosynthesis genes based on shDusp18 and shCtrl MC38 cells (n = 3). h GSEA analysis for cholesterol homeostasis pathway genes in shCtrl versus shDusp18 cells. i qRT-PCR analysis of the indicated cholesterol biosynthetic pathway genes in shDusp18 and shCtrl MC38 cells (n = 3). j Western blot analysis for the indicated proteins in shDusp18 and shCtrl MC38 cells. The IB data are representative of three independent experiments. k Immunoblot (IB) analysis of the indicated proteins in CRCs from AOM/DSS-treated mice, n = 3 independent experiments. l qRT-PCR analysis of the indicated cholesterol biosynthetic pathway genes in CRCs from WT and CKO mice, n = 3 independent experiments. m Heatmap showing differential expression of genes in the cholesterol metabolism and antigen presentation in the proteomics of shCtrl and shDusp18 MC38 cells (n = 3). n Scatterplot showing the correlation between DUSP18 expression levels with those of cholesterol biosynthesis-related genes in TCGA-COAD samples (n = 473). Spearman correlation coefficient (r) and p value are marked. Data are presented as mean ± SD (b, d, i, l). P values were calculated by modified Fisher’s exact tests (e, f), Kolmogorov–Smirnov tests (h), unpaired two-tailed t tests (b, d, l), one-way ANOVA (i) or log-rank (Mantel-Cox) test (c). P values and R were calculated by Spearman’s correlation analysis. Two-sided P value was given (n); ns not significant. Source data are provided as a Source Data file.