Aflatoxin B1 negatively regulates Wnt/?-catenin signaling pathway through activating miR-33a.

ABSTRACT: 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 ?-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 ?-catenin expression when treated at their IC50 values. miR-33a, specifically miR-33a-5p, was demonstrated to down-regulate the expression of ?-catenin, affect the ?-catenin pathway, and inhibit cell growth. Also, by employing a luciferase assay, we found that miR-33a down-regulated ?-catenin by directly binding to the 3'-UTR of ?-catenin. These results suggested that AFB1 might down-regulate ?-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.

SUBMITTER: Fang Y 

PROVIDER: S-EPMC3754916 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature