The results indicated that NT5DC3 efficiently suppressed the development of T2D to colorectal tumors in BALB/c mice, while NT5DC3 protein expression declined during hyperglycemia, and LF inhibited this malignant progression by regulating the levels of NT5DC3 and the PI3K/AKT/mTOR signaling pathways. This evidence concerns the gene NT5DC3 and colorectal neoplasm.