Deficiency of BTB and CNC homology 1 promotes colon tumorigenesis by enhancing intestinal epithelial cell proliferation in mice.

Intestinal epithelial cells serve as the frontline of host defense and function as a physical barrier. BTB and CNC homology 1 (Bach1) is a transcriptional repressor involved in gastrointestinal physiology, but its role in epithelial proliferation and colorectal tumorigenesis remains unclear. This study demonstrates that Bach1 deficiency promotes colonic epithelial proliferation and enhances colorectal tumorigenesis. In Bach1-deficient (Bach1-/-) mice, structural analysis revealed elongation of villi in the small intestine and pronounced changes in the colon, with increased Ki67+ and BrdU+ cells indicating hyperproliferation. In HT-29 colon cancer cells, BACH1 knockdown accelerated cell cycle progression by reducing G0/G1-phase cells and increasing S-phase and G2/M-phase cells, accompanied by upregulation of cell cycle-related genes. Additionally, in an azoxymethane-induced colorectal carcinogenesis model, Bach1-/- mice exhibited a significant increase in aberrant crypt foci formation. These findings suggest that Bach1 deficiency contributes to colorectal tumorigenesis by promoting epithelial hyperproliferation.