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

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Abstract

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.

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Abbreviations

miR:

MicroRNA

COP:

Chlororganic pesticide

EDC:

Endocrine disrupting chemical

DDT:

Dichlorodiphenyltrichloroethane

ER:

Estrogen receptor

CAR:

Constitutive androstane receptor

PBREM:

Phenobarbital-responsive enhancer module

ERE:

Estrogen response element

nt:

Nucleotide

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Acknowledgements

This work is supported by the Russian Science Foundation, Project # 15-15-30012.

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Authors and Affiliations

  1. Institute of Molecular Biology and Biophysics, Timakova str. 2/12, Novosibirsk, 630117, Russia

    Tatiana S. Kalinina, Vladislav V. Kononchuk, Mikhail D. Chanyshev & Lyudmila F. Gulyaeva

  2. Novosibirsk State University, Pirogova str. 2, Novosibirsk, 630090, Russia

    Tatiana S. Kalinina, Mikhail D. Chanyshev & Lyudmila F. Gulyaeva

  3. Institute of Cytology and Genetics, Prospekt Lavrentyeva 10, Novosibirsk, 630090, Russia

    Vladimir Y. Ovchinnikov

Authors
  1. Tatiana S. Kalinina
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  2. Vladislav V. Kononchuk
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Correspondence to Tatiana S. Kalinina.

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All experimental procedures were approved by the Bioethics Committee of the Institute of Molecular Biology and Biophysics and carried out in accordance with Directive 2010/63/EU.

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Kalinina, T.S., Kononchuk, V.V., Ovchinnikov, V.Y. et al. Expression of the miR-190 family is increased under DDT exposure in vivo and in vitro. Mol Biol Rep 45, 1937–1945 (2018). https://doi.org/10.1007/s11033-018-4343-0

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  • DOI: https://doi.org/10.1007/s11033-018-4343-0

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