The effect of xenobiotics on microRNA expression in the rat liver

Abstract

The effect of xenobiotics on microRNA expression in the rat liver has been investigated. Based on results of bioinformatics analysis several microRNAs that can interact with 3'-untranslated regions of cytochrome P450 (CYP) mRNAs have been selected. These included three microRNAs (miR-21, miR-221, miR-222) for CYP1A1 mRNA as a putative target and two microRNAs (miR-143, miR-152) for CYP2B1 mRNA as a putative target. Using the RT-PCR method, expression levels of these microRNAs have been detected in the liver of rats treated with inducers of CYP1A and CYP2B, benzo(a)pyrene (BP), phenobarbital (PB), and DDT. In rats treated with both BP and DDT the hepatic content of miR-21, miR-221 and miR-222 was 2−3 times lower than in the control animals, while ethoxyresorufin-O-deethylase (EROD) activity of CYP1A1 demonstrated a 5.5−8.7-fold increase. In PB-treated rats miR-143 expression remained unchanged, the level of miR-152 increased 2-fold, while pentoxyresorufin-O-deetylase (PROD) activity of CYP2B increased 10.5-fold. In the liver of DDT-treated rats PROD activity demonstrated a 20.8-fold increase; expression of miR-143 increased 2-fold, and miR-152 expression remained unchanged. Bioinformatics analysis of putative miR-target interactions showed that the selected microRNAs can potentially bind such target as AhR, ESR1, GR, CCND1, PTEN mRNAs. Thus, the expression profile of miR-21, miR-221, miR-222, miR-143, miR-152 may vary in dependence on the CYP inducer used. Analysis in silico has shown that besides genes encoding CYP1A/2B other genes including those involved in hormonal carcinogenesis should be considered as potential targets of the investigated microRNAs.