Expression of IRAK-3 is associated with colitis-associated tumorigenesis in mice

Abstract

Interleukin‑1 receptor‑associated kinase‑3 (IRAK‑3) is a negative regulator in Toll‑like receptor (TLR) pathways. The present study investigated the importance of IRAK‑3 in a mouse model of chemically‑induced colitis‑associated tumorigenesis. The colitis‑associated tumorigenesis was induced in ICR mice by the administration of 1,2‑dimethyl hydrazine (DMH) and dextran sodium sulfate (DSS), termed the DMH + DSS group. In the DSS group, mice were administered with DSS; in the DMH group, mice were injected with DMH; in the control group, mice were injected with physiological saline. The clinical signs were examined for 20 weeks; tissue samples were analyzed at week 4, 9, 13 and 20. At week 20, the levels of IRAK‑3 were analyzed using immunohistochemistry, western blot analysis, reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analysis, and methylation‑specific PCR. At week 20, the DMH + DSS group mice exhibited a decrease in total body weight and had developed canalicular adenoma or adenocarcinoma. The mice in the DSS group and DMH group presented with significant colitis at week 20. The mice with colitis‑associated tumorigenesis were found to have decreased levels of IRAK‑3, compared with the mice in the other groups, as evidenced by the results of the immunohistochemistry (P=0.002), RT‑qPCR analysis (P<0.001) and western blot analysis (P<0.001). IRAK‑3 methylation was observed in all experimental groups. Taken together, DMH + DSS induction in colitis led to increased inflammation and risk of tumorigenesis. IRAK‑3 methylation may be a predictive factor in the transition from colitis to cancer.