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

• Published in: Biochemistry (Moscow) Vol. 82; no. 10; pp. 1118 - 1128
• Main Authors: Kalinina, T. S., Kononchuk, V. V., Gulyaeva, L. F.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01-10-2017; Springer; Springer Nature B.V
• Subjects: Activation; Animals; Aromatase - genetics; Aromatase - metabolism; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Carcinogenesis; Carcinogenesis - genetics; Carcinogens; DDT; DDT - toxicity; DEAD-box RNA Helicases - antagonists & inhibitors; DEAD-box RNA Helicases - genetics; DEAD-box RNA Helicases - metabolism; Estrogen Receptor alpha - genetics; Estrogen Receptor alpha - metabolism; Estrogen receptors; Estrogens; Female; Gene expression; Gene Expression Regulation, Neoplastic; Genes; Genetic aspects; Genetic regulation; Health aspects; Insecticides; Life Sciences; Microbiology; MicroRNA; MicroRNAs; MicroRNAs - genetics; miRNA; mRNA; Ovaries; Ovary - drug effects; Ovary - metabolism; Pesticides; PTEN Phosphohydrolase - antagonists & inhibitors; PTEN Phosphohydrolase - genetics; PTEN Phosphohydrolase - metabolism; PTEN protein; Rats; Rats, Wistar; Ribonuclease III - antagonists & inhibitors; Ribonuclease III - genetics; Ribonuclease III - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; Tumor suppressor genes; Uterus; Uterus - drug effects; Uterus - metabolism; microRNAs; hormonal carcinogenesis; DDT; ERα
• ISSN: 0006-2979; 1608-3040
• DOI: 10.1134/S0006297917100042

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.