Pellino 3 promotes the colitis‐associated colorectal cancer through suppression of IRF4‐mediated negative regulation of TLR4 signalling

Abstract

The incidence of colitis‐associated colorectal cancer (CAC) has increased due to a high‐nutrient diet, increased environmental stimuli and inherited gene mutations. To adequately treat CAC, drugs should be developed by identifying novel therapeutic targets. E3 ubiquitin‐protein ligase pellino homolog 3 (pellino 3; Peli3) is a RING‐type E3 ubiquitin ligase involved in inflammatory signalling; however, its role in the development and progression of CAC has not been elucidated. In this study, we studied Peli3‐deficient mice in an azoxymethane/dextran sulphate sodium‐induced CAC model. We observed that Peli3 promotes colorectal carcinogenesis with increased tumour burden and oncogenic signalling pathways. Ablation of Peli3 reduced inflammatory signalling activation at the early stage of carcinogenesis. Mechanistic studies indicate that Peli3 enhances toll‐like receptor 4 (TLR4)‐mediated inflammation through ubiquitination‐dependent degradation of interferon regulatory factor 4, a negative regulator of TLR4 in macrophages. Our study suggests an important molecular link between Peli3 and colonic inflammation‐mediated carcinogenesis. Furthermore, Peli3 can be a therapeutic target in the prevention and treatment of CAC.

Pharmacological Properties of Shionone: Potential Anti-Inflammatory Phytochemical against Different Diseases

“…Anti-inflammation and possible antioxidant activities of shionone inspired researchers to explore its anti-cancer activity, as these activities can contribute to the anti-cancer properties of a compound [ 29 , 30 , 31 ]. One of the important cancers i.e., breast cancer [ 32 , 33 ], was selected to study the anti-cancer effects of shionone through normal breast cell lines and breast cancer cell lines, which were MB-157 and SK-BR-3 cell lines, respectively [ 34 ].…”