Effect of Benzo(a)pyrene on the Expression of miR-483-3p in Hepatocyte Primary Culture and Rat Liver

• Published in: Biochemistry (Moscow) 2019-10, Vol.84 (10), p.1197-1203
• Main Authors: Filippov, S. V., Yarushkin, A. A., Kalinina, T. S., Ovchinnikov, V. Y., Knyazev, R. A., Gulyaeva, L. F.
• Format: Article
• Language: English
• Subjects: Aromatic compounds; Benzo(a)pyrene; Binding sites; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Carcinogens; Chromosome 3; Cytochrome P450; Dioxins; Epigenetics; Estrogens; Gene expression; Hepatocytes; Insulin-like growth factor I; Insulin-like growth factor II; Life Sciences; Liver; Menopause; Microbiology; Pyrene; Transcription
• ISSN: 0006-2979; 1608-3040
• DOI: 10.1134/S0006297919100080

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.