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

<div><p>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 B₁ (AFB₁), a potent mycotoxin. Here, we discovered a novel regulatory network between AFB₁, miR-33a and β-catenin in human carcinoma cells. The level of miR-33a was up-regulated in hepatocellular carcinoma (HCC) cells treated with AFB₁, while in the same cells causing the decrease in β-catenin expression when treated at their IC₅₀ values. miR-33a, specifically miR-33a-5p, was demonstrated to down-regulate the expression of β-catenin, affect the β-catenin pathway, and inhibit cell growth. Also, by employing a luciferase assay, we found that miR-33a down-regulated β-catenin by directly binding to the 3’-UTR of β-catenin. These results suggested that AFB₁ might down-regulate β-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.</p>