MicroRNA Responses to the Genotoxic Carcinogens Aflatoxin B1 and Benzo[a]pyrene in Human HepaRG Cells.
作者： April K. Marrone , Volodymyr Tryndyak , Frederick A. Beland , Igor P. Pogribny
关键词: Cancer research 、 Toxicogenomics 、 Aflatoxin 、 Carcinogen 、 Biology 、 Xenobiotic 、 Bioinformatics 、 Mode of action 、 microRNA 、 Pyrene 、 Benzo(a)pyrene
摘要: Recent advances in toxicogenomics present an opportunity to develop new in vitro testing methodologies identify human carcinogens. We have investigated microRNA expression responses the treatment of liver HepaRG cells with genotoxic carcinogens aflatoxin B1 (AFB1) and benzo[a]pyrene (B[a]P), structurally similar compounds B2 (AFB2) benzo[e]pyrene (B[e]P) that exhibit minimal carcinogenic potential. demonstrate AFB1 or B[a]P resulted specific changes miRNAs as compared their non-carcinogenic analogues, particularly a marked over-expression miR-410. An additional novel finding is dose- time-dependent inhibition miR-122 AFB1-treated cells. Mechanistically, AFB1-induced down-regulation was attributed HNF4A/miR-122 regulatory pathway. These results can be used investigate miRNA xenobiotic exposure, illustrate existence early non-genotoxic events, addition well-established mode action changes, mechanism carcinogenicity.
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