Effect of benzo(a)pyrene on the expression of AhR-regulated microRNA in female and male rat lungs

   
Filippov S.V.1 , Yarushkin A.A.2, Yakovleva A.K.2, Kozlov V.V.3, Gulyaeva L.F.2

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
Section: Experimental Study
DOI: 10.18097/PBMC20206603224      PubMed Id: 32588828
Year: 2020  Volume: 66  Issue: 3  Pages: 224-232
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.
Download PDF:
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.
References  
 2020 (vol 66)
 2019 (vol 65)
 2018 (vol 64)
 2017 (vol 63)
 2016 (vol 62)
 2015 (vol 61)
 2014 (vol 60)
 2013 (vol 59)
 2012 (vol 58)
 2011 (vol 57)
 2010 (vol 56)
 2009 (vol 55)
 2008 (vol 54)
 2007 (vol 53)
 2006 (vol 52)
 2005 (vol 51)
 2004 (vol 50)
 2003 (vol 49)