title: Aflatoxin B1 negatively regulates Wnt/β-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 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.
authors.affiliation: The Ministry of Education Key Laboratory of Biopesticide and Chemical Biology and the College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, P. R. China ; Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, P. R. China ; Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, P. R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Fang
authors.forename: Youjun
authors.initials: Y
authors.lastname: Feng
authors.forename: Tongjin
authors.initials: T
authors.lastname: Wu
authors.forename: Swaminath
authors.initials: S
authors.lastname: Srinivas
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Yang
authors.forename: Jue
authors.initials: J
authors.lastname: Fan
authors.forename: Chi
authors.initials: C
authors.lastname: Yang
authors.forename: Shihua
authors.initials: S
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions; D016604:Aflatoxin B1 / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011042:Poisons / Q000494:pharmacology*; D012334:RNA, Neoplasm / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051176:beta Catenin / Q000096:biosynthesis*
chemical_list: D020413:3' Untranslated Regions; C550416:MIRN33a microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D011042:Poisons; D012334:RNA, Neoplasm; D051153:Wnt Proteins; D051176:beta Catenin; D016604:Aflatoxin B1