Fig. 2: Activation of viral mimicry by DNA hypomethylation inhibits colitis-associated cancer.

a Relative expression of transposable elements in colonic epithelial cells isolated from control (n = 3) and DSS-treated mice (n = 5). Data was analyzed using an unpaired two-tailed Student’s t-test. b Relative mRNA expression of Ifnα, Ifnβ, and Isg15 in whole colonic tissues from C57Bl6/J mice treated with DSS (n = 4) compared to controls (n = 3). Data was analyzed using an unpaired two-tailed Student’s t-test. c Schematic illustration of the treatment of C57Bl6/J mice with 10 mg/kg AOM, 2.5% DSS, and 5 mg/kg 5-AZA or vehicle. d Representative macroscopic images of colons from AOM/DSS mice treated with 5-AZA or vehicle. White circles represent tumors. Average tumor number (e) and size in mm² (f) in vehicle (n = 7) and 5-AZA (n = 6) treated mice. Each dot indicates the average tumor number/size in an individual mouse. Data was analyzed using an unpaired two-tailed Student’s t-test. g Percentage 5-mC (5-mC/total DNA) in colonic epithelial cells from C57Bl6/J mice treated with two doses of 5 mg/kg 5-AZA (n = 5) or vehicle (n = 3). Data was analyzed using an unpaired two-tailed Student’s t-test. h H&E of colonic tumors from 5-AZA and vehicle-treated mice. Scale bar = 200 μm. i Schematic representation of the treatment of Dclk1^CreERT2;Rosa26^mTmG;Apc^f/f mice with tamoxifen (6 mg p.o. q2d × 3 doses), 2.5% DSS, and 5 mg/kg 5-AZA or vehicle. j Representative macroscopic images of colons from 5-AZA or vehicle-treated Dclk1^CreERT2;Rosa26^mTmG;Apc^f/f mice. White circles represent tumors. k Percentage of mice with tumors in 5-AZA (n = 10) and vehicle treated Dclk1^CreERT2;Rosa26^mTmG;Apc^f/f mice (n = 13). Data was analyzed using a two-sided Fisher’s exact test. l Number of tumors per mouse in 5-AZA and vehicle-treated Dclk1^CreERT2;Apc^f/f mice (n = 6 in each group). Data was analyzed using an unpaired two-tailed Student’s t-test. m Average tumor size per mouse in mm² between 5-AZA (n = 3) and vehicle treated Dclk1^CreERT2;Apc^f/f mice (n = 6). Data was analyzed using an unpaired two-tailed Student’s t-test. n Relative expression of transposable elements in whole colonic tissues from 5-AZA (n ≥ 4) and vehicle-treated Dclk1^CreERT2;Apc^f/f mice (n ≥ 4). Data was analyzed using an unpaired two-tailed Student’s t-test. o Relative mRNA expression of Ifnα, Ifnβ, Ifnλ2/3, Isg15, Jak1, Stat1, and Stat2 in whole colonic tissues from 5-AZA (n ≥ 4) and vehicle treated Dclk1^CreERT2;Apc^f/f mice (n≥3). Data was analyzed using an unpaired two-tailed Student’s t-test. Data in all bar graphs are represented as mean ± SEM, and dots represent biologically independent animals. Source data are provided as a Source Data file.