Epithelial Regnase-1 inhibits colorectal tumor growth by regulating IL-17 signaling via degradation of NFKBIZ mRNA

Abstract

Regnase-1, a messenger RNA (mRNA)-degrading enzyme, plays a critical role in regulating inflammation in immune cells. In the current study, its role in intestinal epithelial cells during tumorigenesis has been revealed. Using an original mouse model, loss of Regnase-1 in the epithelium was demonstrated to promote colon tumor growth via enhanced interleukin (IL)-17 signaling, mediated through Nfkbiz, a direct degradative target of Regnase-1. Moreover, a pharmacologic approach using dimethyl fumarate, a potential inhibitor of Regnase-1 protein inactivation, effectively suppressed tumor progression. Clinical data further link low Regnase-1 expression to poor prognosis in colorectal cancer. These findings uncover a protective function of Regnase-1 in the gut epithelium and highlight it as a potential therapeutic target in colorectal tumorigenesis.