TY - JOUR

T1 - Expression of hormonal carcinogenesis genes and related regulatory microRNAs in uterus and ovaries of DDT-treated female rats

AU - Kalinina, T. S.

AU - Kononchuk, V. V.

AU - Gulyaeva, L. F.

N1 - Publisher Copyright: © 2017, Pleiades Publishing, Ltd.

PY - 2017/10/1

Y1 - 2017/10/1

N2 - The insecticide dichlorodiphenyltrichloroethane (DDT) is a nonmutagenic xenobiotic compound able to exert estrogen-like effects resulting in activation of estrogen receptor-α (ERα) followed by changed expression of its downstream target genes. In addition, studies performed over recent years suggest that DDT may also influence expression of microRNAs. However, an impact of DDT on expression of ER, microRNAs, and related target genes has not been fully elucidated. Here, using real-time PCR, we assessed changes in expression of key genes involved in hormonal carcinogenesis as well as potentially related regulatory oncogenic/tumor suppressor microRNAs and their target genes in the uterus and ovaries of female Wistar rats during single and chronic multiple-dose DDT exposure. We found that applying DDT results in altered expression of microRNAs-221, -222, -205, -126a, and -429, their target genes (Pten, Dicer1), as well as genes involved in hormonal carcinogenesis (Esr1, Pgr, Ccnd1, Cyp19a1). Notably, Cyp19a1 expression seems to be also regulated by microRNAs-221, -222, and -205. The data suggest that epigenetic effects induced by DDT as a potential carcinogen may be based on at least two mechanisms: (i) activation of ERα followed by altered expression of the target genes encoding receptor Pgr and Ccnd1 as well as impaired expression of Cyp19a1, affecting, thereby, cell hormone balance; and (ii) changed expression of microRNAs resulting in impaired expression of related target genes including reduced level of Cyp19a1 mRNA.

AB - The insecticide dichlorodiphenyltrichloroethane (DDT) is a nonmutagenic xenobiotic compound able to exert estrogen-like effects resulting in activation of estrogen receptor-α (ERα) followed by changed expression of its downstream target genes. In addition, studies performed over recent years suggest that DDT may also influence expression of microRNAs. However, an impact of DDT on expression of ER, microRNAs, and related target genes has not been fully elucidated. Here, using real-time PCR, we assessed changes in expression of key genes involved in hormonal carcinogenesis as well as potentially related regulatory oncogenic/tumor suppressor microRNAs and their target genes in the uterus and ovaries of female Wistar rats during single and chronic multiple-dose DDT exposure. We found that applying DDT results in altered expression of microRNAs-221, -222, -205, -126a, and -429, their target genes (Pten, Dicer1), as well as genes involved in hormonal carcinogenesis (Esr1, Pgr, Ccnd1, Cyp19a1). Notably, Cyp19a1 expression seems to be also regulated by microRNAs-221, -222, and -205. The data suggest that epigenetic effects induced by DDT as a potential carcinogen may be based on at least two mechanisms: (i) activation of ERα followed by altered expression of the target genes encoding receptor Pgr and Ccnd1 as well as impaired expression of Cyp19a1, affecting, thereby, cell hormone balance; and (ii) changed expression of microRNAs resulting in impaired expression of related target genes including reduced level of Cyp19a1 mRNA.

KW - DDT

KW - ERα

KW - hormonal carcinogenesis

KW - microRNAs

KW - CELLS

KW - INCREASES

KW - MIR-205

KW - HUMAN BREAST-CANCER

KW - TUMORS

KW - ROLES

KW - CLINICAL-APPLICATIONS

KW - ESTROGEN-RECEPTOR-ALPHA

KW - AROMATASE

KW - ER alpha

UR - http://www.scopus.com/inward/record.url?scp=85031761146&partnerID=8YFLogxK

U2 - 10.1134/S0006297917100042

DO - 10.1134/S0006297917100042

M3 - Article

C2 - 29037132

AN - SCOPUS:85031761146

VL - 82

SP - 1118

EP - 1128

JO - Biochemistry (Moscow)

JF - Biochemistry (Moscow)

SN - 0006-2979

IS - 10

ER -