Tissue-specific effects of benzo[a]pyrene and DDT on microRNA expression profile in female rats
Many xenobiotics in the human environment, such as benzo[a]pyrene (B(a)P) and dichlorodiphenyltrichloroethane (DDT), may act as non-genotoxic carcinogens through epigenetic mechanisms, including changes in microRNA expression profile. In part, such disorders can be mediated by the activation of nucl...
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Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders
2018-04-01
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| Series: | Вавиловский журнал генетики и селекции |
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| Online Access: | https://vavilov.elpub.ru/jour/article/view/1451 |
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| author | D. S. Ushakov T. S. Kalinina A. S. Dorozhkova V. Y. Ovchinnikov L. F. Gulyaeva |
| author_facet | D. S. Ushakov T. S. Kalinina A. S. Dorozhkova V. Y. Ovchinnikov L. F. Gulyaeva |
| author_sort | D. S. Ushakov |
| collection | DOAJ |
| description | Many xenobiotics in the human environment, such as benzo[a]pyrene (B(a)P) and dichlorodiphenyltrichloroethane (DDT), may act as non-genotoxic carcinogens through epigenetic mechanisms, including changes in microRNA expression profile. In part, such disorders can be mediated by the activation of nuclear receptors, resulting in the activation of protein coding gene expression and microRNAs involved in malignant transformation of cells. Therefore, the aim of this study was to investigate the chain of events “xenobiotic administration – receptor activation – up-regulating microRNA expression – down-regulation target genes expression” as one of the key factors in the chemically-induced carcinogenesis. Using in silico methods, an analysis of the rat genome was carried out to find microRNAs putatively regulated by AhR (aryl hydrocarbon receptor) and CAR (constitutive androstane receptor), activated by BP and DDT, respectively. In particular, miR-3577 and -193b were selected as potentially regulated CAR, miR-207 was selected as a candidate for miR under AhR regulation. The results of the study showed that the treatment of female rats with DDT and B(a)P caused a tissue-specific changes in the expression of microRNAs and host genes in both acute and chronic administration of xenobiotics. To confirm the effects of xenobiotics on the microRNA expression, we also estimated the mRNA level of PTPN6, EIF3F, Cbx7, and Dicer1 genes potentially targeting miR-193b, -207, and -3577. The study has shown a high correlation between the expression of target genes and microRNAs; however these changes depended on the tissue types, the dose and time after xenobiotic treatment. |
| format | Article |
| id | doaj-art-99469aa1ea124b269bfad4f473e05d50 |
| institution | Kabale University |
| issn | 2500-3259 |
| language | English |
| publishDate | 2018-04-01 |
| publisher | Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders |
| record_format | Article |
| series | Вавиловский журнал генетики и селекции |
| spelling | doaj-art-99469aa1ea124b269bfad4f473e05d502025-02-01T09:58:05ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592018-04-0122224825510.18699/VJ18.355748Tissue-specific effects of benzo[a]pyrene and DDT on microRNA expression profile in female ratsD. S. Ushakov0T. S. Kalinina1A. S. Dorozhkova2V. Y. Ovchinnikov3L. F. Gulyaeva4Institute of Molecular Biology and Biophysics; Novosibirsk State Pedagogical University,Institute of Molecular Biology and Biophysics; Novosibirsk State UniversityInstitute of Molecular Biology and BiophysicsInstitute of Cytology and Genetics SB RASInstitute of Molecular Biology and Biophysics; Novosibirsk State Pedagogical University; Novosibirsk State UniversityMany xenobiotics in the human environment, such as benzo[a]pyrene (B(a)P) and dichlorodiphenyltrichloroethane (DDT), may act as non-genotoxic carcinogens through epigenetic mechanisms, including changes in microRNA expression profile. In part, such disorders can be mediated by the activation of nuclear receptors, resulting in the activation of protein coding gene expression and microRNAs involved in malignant transformation of cells. Therefore, the aim of this study was to investigate the chain of events “xenobiotic administration – receptor activation – up-regulating microRNA expression – down-regulation target genes expression” as one of the key factors in the chemically-induced carcinogenesis. Using in silico methods, an analysis of the rat genome was carried out to find microRNAs putatively regulated by AhR (aryl hydrocarbon receptor) and CAR (constitutive androstane receptor), activated by BP and DDT, respectively. In particular, miR-3577 and -193b were selected as potentially regulated CAR, miR-207 was selected as a candidate for miR under AhR regulation. The results of the study showed that the treatment of female rats with DDT and B(a)P caused a tissue-specific changes in the expression of microRNAs and host genes in both acute and chronic administration of xenobiotics. To confirm the effects of xenobiotics on the microRNA expression, we also estimated the mRNA level of PTPN6, EIF3F, Cbx7, and Dicer1 genes potentially targeting miR-193b, -207, and -3577. The study has shown a high correlation between the expression of target genes and microRNAs; however these changes depended on the tissue types, the dose and time after xenobiotic treatment.https://vavilov.elpub.ru/jour/article/view/1451micrornatarget-geneshost-genesqpcr-rtbioinformaticsin silicomolecular biologyrna interference |
| spellingShingle | D. S. Ushakov T. S. Kalinina A. S. Dorozhkova V. Y. Ovchinnikov L. F. Gulyaeva Tissue-specific effects of benzo[a]pyrene and DDT on microRNA expression profile in female rats Вавиловский журнал генетики и селекции microrna target-genes host-genes qpcr-rt bioinformatics in silico molecular biology rna interference |
| title | Tissue-specific effects of benzo[a]pyrene and DDT on microRNA expression profile in female rats |
| title_full | Tissue-specific effects of benzo[a]pyrene and DDT on microRNA expression profile in female rats |
| title_fullStr | Tissue-specific effects of benzo[a]pyrene and DDT on microRNA expression profile in female rats |
| title_full_unstemmed | Tissue-specific effects of benzo[a]pyrene and DDT on microRNA expression profile in female rats |
| title_short | Tissue-specific effects of benzo[a]pyrene and DDT on microRNA expression profile in female rats |
| title_sort | tissue specific effects of benzo a pyrene and ddt on microrna expression profile in female rats |
| topic | microrna target-genes host-genes qpcr-rt bioinformatics in silico molecular biology rna interference |
| url | https://vavilov.elpub.ru/jour/article/view/1451 |
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