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Expression of the miR-190 family is increased under DDT exposure in vivo and in vitro

Kalinina, Tatiana S., Kononchuk, Vladislav V., Ovchinnikov, Vladimir Y., Chanyshev, Mikhail D., Gulyaeva, Lyudmila F.
Molecular biology reports 2018 v.45 no.6 pp. 1937-1945
DDT (pesticide), animal ovaries, endometrium, females, humans, insecticides, liver, mammary glands, mechanism of action, messenger RNA, microRNA, rats, receptors
A non-genotoxic insecticide dichlorodiphenyltrichloroethane (DDT), can affect mRNA and microRNA levels, however, its precise mechanism of action remains poorly understood. Using in silico methods we found that the rat miR-190 family is potentially regulated by CAR and ER receptors activated by DDT. We showed that exposure to DDT results in a dose- and organ-dependent increase in the expression of miR-190a, -190b in the liver, uterus, ovaries and mammary gland of female Wistar rats. Additionally, we demonstrate a decrease in protein product level of Tp53inp1, the target gene of these microRNAs, in the rat uterus. It is known that miR-190 is probably regulated by ER in humans, thus we measured the level of miR-190a, -190b in primary cultures of malignant and normal human endometrial cells treated with different doses of DDT. We detected an increase in miR-190b level in normal endometrial cells under DDT exposure. Thus, our results indicate that DDT exposure lead to change in the expression of oncogenic miR-190 family and its target gene Tp53inp1 which may be due to activation of CAR and ER.