TY - JOUR

T1 - The search of CAR, AhR, ESRs binding sites in promoters of intronic and intergenic microRNAs

AU - Ovchinnikov, Vladimir Y.

AU - Antonets, Denis V.

AU - Gulyaeva, Lyudmila F.

PY - 2018/2/1

Y1 - 2018/2/1

N2 - MicroRNAs (miRNAs) play important roles in the regulation of gene expression at the post-transcriptional level. Many exogenous compounds or xenobiotics may affect microRNA expression. It is a well-established fact that xenobiotics with planar structure like TCDD, benzo(a)pyrene (BP) can bind aryl hydrocarbon receptor (AhR) followed by its nuclear translocation and transcriptional activation of target genes. Another chemically diverse group of xenobiotics including phenobarbital, DDT, can activate the nuclear receptor CAR and in some cases estrogen receptors ESR1 and ESR2. We hypothesized that such chemicals can affect miRNA expression through the activation of AHR, CAR, and ESRs. To prove this statement, we used in silico methods to find DRE, PBEM, ERE potential binding sites for these receptors, respectively. We have predicted AhR, CAR, and ESRs binding sites in 224 rat, 201 mouse, and 232 human promoters of miRNA-coding genes. In addition, we have identified a number of miRNAs with predicted AhR, CAR, and ESRs binding sites that are known as oncogenes and as tumor suppressors. Our results, obtained in silico, open a new strategy for ongoing experimental studies and will contribute to further investigation of epigenetic mechanisms of carcinogenesis.

AB - MicroRNAs (miRNAs) play important roles in the regulation of gene expression at the post-transcriptional level. Many exogenous compounds or xenobiotics may affect microRNA expression. It is a well-established fact that xenobiotics with planar structure like TCDD, benzo(a)pyrene (BP) can bind aryl hydrocarbon receptor (AhR) followed by its nuclear translocation and transcriptional activation of target genes. Another chemically diverse group of xenobiotics including phenobarbital, DDT, can activate the nuclear receptor CAR and in some cases estrogen receptors ESR1 and ESR2. We hypothesized that such chemicals can affect miRNA expression through the activation of AHR, CAR, and ESRs. To prove this statement, we used in silico methods to find DRE, PBEM, ERE potential binding sites for these receptors, respectively. We have predicted AhR, CAR, and ESRs binding sites in 224 rat, 201 mouse, and 232 human promoters of miRNA-coding genes. In addition, we have identified a number of miRNAs with predicted AhR, CAR, and ESRs binding sites that are known as oncogenes and as tumor suppressors. Our results, obtained in silico, open a new strategy for ongoing experimental studies and will contribute to further investigation of epigenetic mechanisms of carcinogenesis.

KW - cancer

KW - miRNA

KW - xenobiotics; nuclear receptors

KW - nuclear receptors

KW - xenobiotics

KW - APOPTOSIS

KW - MOUSE

KW - RECEPTOR

KW - PROLIFERATION

KW - CANCER

KW - GENE

KW - GROWTH

KW - TUMOR-SUPPRESSOR

KW - EXPRESSION

KW - MicroRNAs/genetics

KW - Computational Biology/methods

KW - Estrogen Receptor beta/metabolism

KW - Computer Simulation

KW - Binding Sites

KW - Promoter Regions, Genetic

KW - Response Elements

KW - Introns

KW - Estrogen Receptor alpha/metabolism

KW - Rats

KW - Receptors, Aryl Hydrocarbon/metabolism

KW - Receptors, Cytoplasmic and Nuclear/metabolism

KW - Animals

KW - Xenobiotics/metabolism

KW - Mice

KW - Software

UR - http://www.scopus.com/inward/record.url?scp=85040044472&partnerID=8YFLogxK

U2 - 10.1142/S0219720017500299

DO - 10.1142/S0219720017500299

M3 - Article

C2 - 29301444

AN - SCOPUS:85040044472

VL - 16

JO - Journal of Bioinformatics and Computational Biology

JF - Journal of Bioinformatics and Computational Biology

SN - 0219-7200

IS - 1

M1 - 1750029

ER -