Cell cycle dysregulation: a central hub in colitis-associated colorectal carcinogenesis.

The process of developing from inflammatory bowel disease (IBD) to colorectal cancer (CRC) depends on the dysregulation of the core cell cycle network. Single-cell omics studies have revealed a significant difference: malignant colorectal cancer cells are mainly in the G2/M phase, while epithelial cells in inflammatory bowel disease (IBD) exhibit G1 phase arrest or excessive proliferation - this indicates that during chronic inflammation, the original cell cycle of precancerous cells has already become dysregulated. Among the key signaling pathways, such as Rb-E2F, NF-κB, JAK-STAT and Hippo-YAP, jointly regulate the cell cycle system. Including cyclins D1, A2 and B1 and their cyclin-dependent kinases (CDKs), as well as cyclin-dependent kinase inhibitors (such as p21, p27, p57), jointly regulate intestinal tumor cells and tumor immune escape. Therefore, this review elaborates on the key interactions between ROS and the cell cycle/cyclin/CDK axis, and explains in detail how oxidative stress and DNA damage disrupt cell cycle checkpoints, thereby driving the growth, invasion, metastasis and immune escape of intestinal tumors. In conclusion, for the regulation of the cell cycle during the "inflammation-cancer" transformation process in colorectal cancer, new targets and reasonable combination strategies have been proposed.