Aflatoxin B1 Negatively Regulates Wnt/β-Catenin Signaling Pathway through Activating miR-33a

MicroRNAs are known to play an important role in modulating gene expression in various diseases including cancers and cardiovascular disorders, but only a few of them are associated with the pathology of aflatoxin B-1 (AFB(1)), a potent mycotoxin. Here, we discovered a novel regulatory network between AFB(1), miR-33a and beta-catenin in human carcinoma cells. The level of miR-33a was up-regulated in hepatocellular carcinoma (HCC) cells treated with AFB(1), while in the same cells causing the decrease in beta-catenin expression when treated at their IC50 values. miR-33a, specifically miR-33a-5p, was demonstrated to down-regulate the expression of beta-catenin, affect the beta-catenin pathway, and inhibit cell growth. Also, by employing a luciferase assay, we found that miR-33a down-regulated beta-catenin by directly binding to the 3'-UTR of beta-catenin. These results suggested that AFB(1) might down-regulate beta-catenin by up-regulating miR-33a. This understanding opens new lines of thought in the potential role of miR-33a in the clinical therapy of cancer.