TY - JOUR

T1 - Effect of Benzo(a)pyrene on the Expression of miR-483-3p in Hepatocyte Primary Culture and Rat Liver

AU - Filippov, S. V.

AU - Yarushkin, A. A.

AU - Kalinina, T. S.

AU - Ovchinnikov, V. Y.

AU - Knyazev, R. A.

AU - Gulyaeva, L. F.

PY - 2019/10/1

Y1 - 2019/10/1

N2 - 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.

AB - 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.

KW - AhR

KW - benzo(a)pyrene

KW - DRE

KW - ERα

KW - induction

KW - microRNA

KW - target genes

KW - BREAST-CANCER

KW - ARYL-HYDROCARBON RECEPTOR

KW - ALPHA

KW - IDENTIFICATION

KW - ER alpha

UR - http://www.scopus.com/inward/record.url?scp=85073598641&partnerID=8YFLogxK

U2 - 10.1134/S0006297919100080

DO - 10.1134/S0006297919100080

M3 - Article

C2 - 31694515

AN - SCOPUS:85073598641

VL - 84

SP - 1197

EP - 1203

JO - Biochemistry (Moscow)

JF - Biochemistry (Moscow)

SN - 0006-2979

IS - 10

ER -