MicroRNA-449a is a potential predictor of colitis-associated colorectal cancer progression

An early diagnosis of colitis-associated colorectal cancer (CAC) is important for its clinical management. However, it is currently difficult to distinguish the different stages of CAC development. MicroRNA dysregulation is common in human colorectal disorders, however little is known regarding whether miRNA affects tumor progression by regulating inflammation. In the present study, we identified a novel miRNA (miR-449a), the expression of which was significantly reduced in CAC tissues than in paired adjacent non-cancerous tissues (ANTs). Notably, the level of miR-449a was in a markedly decreased pattern during the neoplastic transformation of ulcerative colitis (UC)-to-CAC, as demonstrated by both clinical investigations and the experimental mouse model induced by AOM/DSS treatment. In addition, we observed that decreased miR-449a expression was associated with advanced T or N status, later clinical stage and poor histological differentiation of CAC. Mechanistic studies revealed that miR-449a inhibited the growth and metastasis of human colon cancer cells by directly binding to the 3-UTR of Notch-1 and thereby, suppressed the activation of the Notch signaling pathway. Therefore, these findings provide strong evidence for the translational potential of miR-449a in the discrimination of patients with UC that is likely to progress into CAC, from those unlikely to progress, as well as in the prognosis and diagnosis of CAC.