Using bioinformatics analysis we selected microRNAs which could bind 3'-UTR-region of cytochrome P450 (CYP) genes. Three microRNA miR-21, -221, -222, their potential targets might be mRNA for CYP1A1, and two microRNA miR-143, miR-152 for CYP2B1 accordingly were selected for experimental verification. Expression level of these microRNAs in rat liver upon benzo(a)pyrene (BP), phenobarbital (PB), and DDT induction was determined using RT-qPCR method. In rats treated by both BP, and DDT the hepatic content of miR-21, -221, -222 significantly demonstrated a 2-3-fold decrease. The decrease in miR expression was accompanied by a considerable (5.5-8.7-fold) increase in the CYP1A1-mediated EROD activity. The expression of miR-143 remained unchanged after the PB treatment, while the expression of miR-152 increased by 2 times, however, the (10.5-fold) increase in PROD activity of CYP2B was much higher. In the DDT-treated liver PROD activity increased by 20 times, the expression of miR-152 didn't change, and the expression of miR-143 increased by 2 times. The bioinformatics analysis of interactions between microRNAs and targets showed that the studied miRs can potentially bind 3'-end of AhR, ESR1, GR, CCND1, PTEN mRNA. Thus, the expression profile of miR-21, -221, -222, -143, -152 might change under the xenobiotics exposure. In silico analysis confirmed, that microRNAs target not only cytochrome P450 mRNA but also other genes, including those involved in hormonal carcinogenesis, they also can be regulated with studied miRs.
Issledovano vliianie ksenobiotikov na ékspressiiu mikroRNK v pecheni krys. S étoĭ tsel'iu s pomoshch'iu bioinformaticheskogo analiza byli otobrany mikroRNK, sposobnye vzaimodeĭstvovat' s 3'-netransliruemoĭ oblast'iu (3'-UTR) mRNK genov tsitokhroma R450 (CYP) - tri mikroRNK (miR-21, -221, -222), potentsial'nymi misheniami kotorykh iavliaiutsia mRNK SYP1A1 i dve mikroRNK (miR-143, miR-152), deĭstvuiushchie na mRNK CYP2B1. Metodom OT-PTsR v real'nom vremeni opredelen uroven' ékspressii dannykh mikroRNK v pecheni krys posle obrabotki induktorami tsitokhroma R450 CYP1A i CYP2B - benzo(a)pirenom (BP), fenobarbitalom (FB) i DDT. Soderzhanie miR-21,-221,-222 v pecheni krys, obrabotannykh kak BP, tak i DDT, bylo v 2-3 raza nizhe, chem u kontrol'nykh zhivotnykh, a étoksirezorufin-O-deétilaznaia (ÉROD) aktivnost' CYP1A1 - uvelichena v 5,5-8,7 raza. Pod deĭstviem FB ékspressiia miR-143 ne izmenilas', a miR-152 uvelichilas' v 2 raza, togda kak pentoksirezorufin-O-deétilaznaia (PROD) aktivnost' CYP2B uvelichilas' v 10,5 raz. V pecheni krys, obrabotannykh DDT, aktivnost' PROD uvelichilas' v 20,8 raza, ékspressiia miR-143 - v 2 raza, a miR-152 ne izmenilas'. Bioinformaticheskiĭ analiz vzaimodeĭstviĭ mikroRNK-mishen' pokazal, chto otobrannye mikroRNK potentsial'no sposobny sviazyvat' takie misheni, kak mRNK AhR, ESR1, GR, CCND1, PTEN. Takim obrazom, profil' ékspressii miR-21, -221, -222, -143, -152 mozhet meniat'sia v zavisimosti ot primeniaemogo induktora CYP. Kak pokazal analiz in silico, misheniami issleduemykh mikroRNK mogut byt' ne tol'ko CYP1A/2B, no i drugie geny, v tom chisle vovlechennye v gormonal'nyĭ kantserogenez.
Keywords: DDT; benzo(a)pyrene; cytochrome P450; induction; microRNA; phenobarbital.