Regulation of NLRP3/TRIM family signaling in gut inflammation and colorectal cancer

Abstract

CRC (Colorectal cancer) ranks among the most prevalent tumors in humans and remains a leading cause of cancer-related mortality worldwide. Numerous studies have highlighted the connection between inflammasome over-activation and the initiation and progression of CRC. The activation of the NLRP3 (NOD-like receptor family, pyrin domain containing 3) inflammasome is dependent on the nuclear NF-kβ (Nuclear Factor kappa-light-chain-enhancer of activated B cells) pathway, leading to the maturation and release of inflammatory cytokines such as IL-1ß (Interleukin 1 beta) and IL-18 (Interleukin 18). While inflammation is crucial for defense mechanisms and tissue repair, excessive information can pose significant risks. Mounting evidence suggests that overactivation of the inflammasome contributes to the pathogenesis of inflammatory diseases. Consequently, there is a concerted effort to tightly regulate inflammasome activity and mitigate excessive inflammatory responses, particularly in conditions such as IBD (Inflammatory Bowel Disease), which includes Ulcerative Colitis and Crohn's Disease. The tripartite motif (TRIM) protein family, characterized by a conserved structure and rapid evolutionary diversification, includes members with critical roles in ubiquitination and other regulatory functions. Their importance in modulating inflammatory responses is widely acknowledged. This article aims to investigate the interplay between TRIM proteins and the NLRP3 Inflammasome in CRC and gut inflammation, offering insights for future research endeavors and potential therapeutic strategies.