One‐carbon Metabolism Related B‐vitamins Alter the Expression of microRNAs Associated with the Wnt Pathway in Mouse Colonic Epithelium

Abstract

MicroRNAs regulate numerous biological processes and thereby contribute to a variety of diseases including cancer. One‐carbon metabolism related B‐vitamins (folate, B2, B6, B12) have been indicated to influence the expression of a variety of genes, likely via their role in biological methylation. This study investigated whether these vitamins alter the expression of Wnt‐signaling related microRNAs and thereby influence intestinal tumorigenesis. MicroRNA expression profiles were measured using microRNA arrays on colonic epithelial cells from Apc1638N mice fed with diets deplete or sufficient in those vitamins. 38 Wnt pathway‐related microRNAs were also examined by real‐time PCR. 6 microRNAs in a total of 609 were identified to be significantly altered by those vitamin depletion (p<0.05) with additional 11 microRNAs having a mild degree of alterations (p<0.10). Among the 38 Wnt pathway‐related microRNAs, the expressions of 4 microRNAs were altered (p<0.05). The microRNA array data with the validation of Wnt pathway‐related microRNAs collectively indicate that the expressions of miR‐21 and miR‐122, which are biologically linked, miR‐29 family and miR‐34 family are dysregulated by those B‐vitamin depletion. In summary, these findings indicate that microRNAs may constitue a mechanism by which one‐carbon B‐vitamins regulate the Wnt‐signaling.