1. Institute of Molecular Biology and Biophysics, Federal Research Center of Fundamental and Translational Medicine, Novosibirsk, Russia; Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia 2. Institute of Molecular Biology and Biophysics, Federal Research Center of Fundamental and Translational Medicine, Novosibirsk, Russia; Novosibirsk State University, Novosibirsk, Russia; 3. Institute of Molecular Biology and Biophysics, Federal Research Center of Fundamental and Translational Medicine, Novosibirsk, Russia; Novosibirsk Regional Oncology Center, Novosibirsk, Russia
Smoking is the main risk factor for lung cancer, mainly due to presence of nitrosamines and polycyclic aromatic hydrocarbons, including benzo[a]pyrene (BP) in tobacco smoke composition. The genotoxic effect of BP is based on the high DNA-binding ability of its metabolites, while the epigenetic effects are mediated by a change in the expression of cancer related genes or regulatory RNAs. It has been shown that women have a higher risk to develop lung cancer upon smoking rather than men. We hypothesized that crosstalk between signaling pathways activated by BP and estrogens could underlie the sex-dependent differences in miRNAs expression. To test this hypothesis, male and female rats were subjected to short-term or long-term BP exposure. Using in silico analysis, miRNAs containing the ER- and AhR-binding sites in the promoters of the genes (or host genes) were selected. During chronic exposure of BP the expression of miR-22-3p, -29a-3p, -126a-3p, -193b-5p in the lungs of male rats were significantly increased, while the level of miRNA-483-3p were decreased. Expression of miRNA-483-3p was up-regulated during chronic BP exposure in the lungs of female rats and the levels of other studied miRNAs were unchanged. In turn, changes in the expression of miRNAs were followed by changes in the expression of their target genes, including PTEN, EMP2, IGF1, ITGA6, SLC34A2, and the observed changes in female and male rat lungs were varied. Thus, our results suggest that sex-dependent epigenetic effects of BP may be based on different expression of AhR- and ER- regulated miRNAs.
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Keywords: benzo(a)pyrene, AhR, ER, microRNA, sex differences
Citation:
Filippov S.V., Yarushkin A.A., Yakovleva A.K., Kozlov V.V., Gulyaeva L.F. (2020) Effect of benzo(a)pyrene on the expression of AhR-regulated microRNA in female and male rat lungs. Biomeditsinskaya Khimiya, 66(3), 224-232.
Filippov S.V. et al. Effect of benzo(a)pyrene on the expression of AhR-regulated microRNA in female and male rat lungs // Biomeditsinskaya Khimiya. - 2020. - V. 66. -N 3. - P. 224-232.
Filippov S.V. et al., "Effect of benzo(a)pyrene on the expression of AhR-regulated microRNA in female and male rat lungs." Biomeditsinskaya Khimiya 66.3 (2020): 224-232.
Filippov, S. V., Yarushkin, A. A., Yakovleva, A. K., Kozlov, V. V., Gulyaeva, L. F. (2020). Effect of benzo(a)pyrene on the expression of AhR-regulated microRNA in female and male rat lungs. Biomeditsinskaya Khimiya, 66(3), 224-232.
International Agency for Research on Cancer (2012) Chemical agents and related occupations, IARC Monogr. Eval. Carcinog. Risks Humans, 100F, 111-138. Scholar google search
Gkountakos A., Sartori G., Falcone I., Piro G., Ciuffreda L., Carbone C., Tortora G., Scarpa A., Bria E., Milella M., Rosell R., Corbo V., Pilotto S. (2019) Cancers (Basel), 11(8), 1141. CrossRef Scholar google search
Wang Y., Cheng H., Ding Y., Chou L., Chow N. (2017) Biochim. Biophys. Acta. Rev. Cancer, 1868(1), 199-211. CrossRef Scholar google search
Brantley E., Callero M., Berardi D., Campbell P., Rowland L., Zylstra D., Amis L., Yee M., Simian M., Todaro L., Loaiza-Perez A., Soto U. (2016) Cancer Lett., 376(1), 53-61. CrossRef Scholar google search
Hong S., Minai-Tehrani A., Chang S., Jiang H., Lee S., Lee A., Seo H., Chae C., Beck G. Jr., Cho M. (2013) PLoS One, 8(10), e77121. CrossRef Scholar google search
Liu R., Zhang Y., Zhang S., Cheng Z., Yu J., Zhou S., Song J. (2019) Eur. Rev. Med. Pharmacol. Sci., 23(2), 679-689. Scholar google search
Zhang Y., Wu L., Wang Y., Zhang M., Li L., Zhu D., Li X., Gu H., Zhang C., Zen K. (2012) J. Biol. Chem., 287(18), 14851-14862. CrossRef Scholar google search
Filippov S., Yarushkin A., Kalinina T., Ovchinnikov V., Knyazev R., Gulyaeva L. (2019) Biochemistry (Moscow), 84(10), 1197-1203. CrossRef Scholar google search
Haetscher N., Feuermann Y., Wingert S., Rehage M., Thalheimer F., Weiser C., Bohnenberger H., Jung K., Schroeder T., Serve H., Oellerich T., Hennighausen L., Rieger M. (2015) Nat. Commun., 6, 8928. CrossRef Scholar google search
Rodríguez-Fragoso L., Melendez K., Hudson L., Lauer F., Burchiel S. (2009) Toxicol. Appl. Pharmacol., 235(3), 321-328. CrossRef Scholar google search
Pérez-Ramírez C., Cañadas-Garre M., Molina M., Faus-Dáder M., Calleja-Hernández M. (2015) Pharmacogenomics., 16(16), 1843-1862. CrossRef Scholar google search
