2Federal Research Center Institute of Cytology and Genetic, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia
3Novosibirsk State University, 630090 Novosibirsk, Russia
4Institute of Biochemistry, Federal Research Center of Fundamental and Translational Medicine, 630117 Novosibirsk, Russia
*To whom correspondence should be addressed.
Received May 21, 2019; Revised June 21, 2019; Accepted June 21, 2019
Here, we suggested that the epigenetic mechanism of benzo(a)pyrene (BP) action might be based on the aryl hydrocarbon receptor (AhR)-mediated transcription of the target genes, including miRNAs, that have the dioxin response element (DRE) in their promoters. The effect of BP on the expression of the oncogenic miR-483-3p, its host gene IGF2, and target gene IGF1 in primary hepatocytes and in the liver of Wistar female rats was investigated. The activation of AhR was confirmed using selective AhR inhibitor CH-223191 and by evaluating expression of the target CYP1A1 gene. The lack of coordination between the expression of miR-483-3p and its host gene IGF2 was revealed, which may be due to the presence of the binding site for the estrogen receptor alpha (ERα), which is a negative expression regulator. Our results confirm the existence of the AhR-mediated pathway in the regulation of expression of miR-483-3p, IGF1, and IGF2 under BP exposure, which is of considerable interest for understanding the epigenetic mechanisms of the carcinogenic effect of BP.
KEY WORDS: benzo(a)pyrene, AhR, ERα, DRE, induction, microRNA, target genes