LAUSR

Inflammatory bowel disease, characterised by chronic relapsing‐remitting colitis, is a significant risk factor for colorectal cancer (CRC). Previously, we showed that miR‐126 functions as a tumour suppressor in CRC and is inversely correlated with tumour proliferation, metastasis and patient prognosis. In the current study, we documented a protective role for miR‐126 in colitis‐associated CRC (CAC) and its underlying mechanism. We detected downregulated miR‐126 expression during colorectal tumorigenesis in the mouse CAC model and in specimens from patients with CRC. The deficiency of miR‐126 in intestinal epithelial cells (IECs) exacerbated tumorigenesis in mice. We identified CXCL12 as a direct target of miR‐126 in inhibiting the development of colitis and CAC. Moreover, miR‐126 regulated the recruitment of macrophages via CXCL12 and decreased the levels of proinflammatory cytokines (IL‐6, IL‐12 and IL‐23). In addition, IL‐6 secreted by macrophages, which were regulated by cocultured transfected CRC cells, altered the proliferation and migration of colon cells. Our data suggest that miR‐126 exerts an antitumour effect on CAC by regulating the crosstalk between IECs and macrophages via CXCL12‐IL‐6 signalling. Our study contributes to the understanding of cancer progression and suggests miR‐126 as a potential therapy for CRC.