MicroRNA-31 (miR-31) is an evolutionarily conserved microRNA, and its biological function in colorectal cancer and other cancers is controversial. In this study, we identified the host gene of mouse miR-31 and found that miR-31 was over-expressed in both human colorectal cancer and mouse colon cancer models. We here developed a miR-31 conditional knockout mouse model that allows for colon epithelium specific deletion of miR-31 to investigate its functionality in colon cancer development. We demonstrated that mice with miR-31 conditional deletion resulted in more severe colitis-associated cancer than wild-type, and we further identified Wdr5 as an important target of miR-31. (C) 2017 Elsevier Inc. All rights reserved.