Effect of xenobiotics on microrna expression in rat liver

Abstract

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

Impacts of Sub-lethal DDT Exposures on microRNA and Putative Target Transcript Expression in DDT Resistant and Susceptible Drosophila melanogaster Strains

“…It was previously shown that miRNA levels are induced or repressed following animal exposures to chemical insecticides. For example, miR-21 , miR-221 , and miR-222 expression levels were estimated to be 2–3 times lower in DDT-treated rat liver compared to untreated controls (Gulyaeva et al, 2016). Recently, analogous levels of differential miRNA expression patterns were associated with insecticide resistance or were shown to be induced following exposure to insecticides.…”

Endocrine disruptors from the environment affecting breast cancer (Review)

“…Another change that DDT can cause at the epigenetic level is the expression of miRNAs. The characterization of miRNA can vary depending on the type of tissue or cells that are analyzed (121). A study performed in rodents showed a significant positive modulation of miRNA in hepatic cells.…”

“…Therefore, it is viable to state that DTT may modulate miRNA for those genes involved in detoxification, such as genes that encode for CYP enzymes. It has been postulated that a plausible mechanism is DNA methylation (121). The available scientific tools, of the modern world, have allowed us to get acceptable evidence of the long-term exposure to DTT and its effects on the biological system.…”

Renal Ca2+ and Water Handling in Response to Calcium Sensing Receptor Signaling: Physiopathological Aspects and Role of CaSR-Regulated microRNAs

“…Distinct mechanisms of regulation of miRNA expression can occur in cell: transcriptional (changes in gene expression and promoter hypermethylation) and post-transcriptional (changes in miRNA processing), as well as effects of endogenous (hormones, cytokines) and exogenous (xenobiotics) compounds on the miRNA expression (reviewed in [105,106]).…”