Abstract
A recent study published in
Nature
reveals that colonic stem cells retain long-term memory via activator protein 1 transcription-factor-mediated epigenetic remodeling following the resolution of inflammation. Chronic inflammation is an established risk factor for cancer; however, the mechanisms through which tissues maintain a memory of inflammatory history to drive malignant transformation after resolution remain largely elusive. This primed state markedly accelerates tumorigenesis upon the acquisition of oncogenic mutations. Chronic inflammation, exemplified by ulcerative colitis, is a key driver of colorectal cancer. Contrary to the classical view that inflammation promotes tumorigenesis via DNA damage, Nagaraja et al. showed that inflammation leaves genomic imprints on colonic stem cells, lowering their threshold for malignant transformation upon subsequent oncogenic stimuli. First discovered in the innate immune system, inflammatory memory has since been confirmed in epithelial barrier cells and stem cells. Research indicates that following inflammatory exposure, cells retain lasting epigenetic imprints through the remodeling of chromatin, which is the complex interaction and also binding product of DNA and proteins. The specific mechanisms may involve alterations in chromatin accessibility and the modification of histones that are proteins that bind to DNA. This discovery provides a feasible approach to investigating the mechanisms underlying the interplay between inflammation, epigenetic memory, and tumorigenesis, deepening our understanding of tumor progression.