In Silico Identification of MicroRNAs Predicted to Regulate the Drug Metabolizing Cytochrome P450 Genes

Anuradha      Ramamoorthy; Todd      C. Skaar

doi:10.2174/187231211795305258

Abstract

Objective: Cytochrome P450 (CYP) enzymes exhibit high interindividual variability that is not completely explained by known environmental and genetic factors. To further understand this variability, we hypothesized that microRNAs (miRNAs) may regulate CYP expression.

Methods: MiRNA identification algorithms were used to identify the miRNAs that are predicted to regulate twelve major drug metabolizing CYPs and to identify polymorphisms in CYP mRNA 3-UTRs that are predicted to interfere with normal mRNA-miRNA interactions.

Results: All twelve CYPs were predicted to be targets of miRNAs. Additionally, 38 SNPs in CYP mRNA 3-UTRs were predicted to interfere with miRNA targeting of mRNAs. These predicted miRNAs and SNPs are candidates for future in vitro studies focused on understanding the molecular regulation of these CYP genes.

Conclusion: These in silico results provide strong support for a role of miRNA in the regulation and variability of CYP expression.

Keywords: Bioinformatic analysis, cytochrome P450s, microRNA, polymorphisms, drug metabolizing enzymes (DMEs), ATP-binding cassette, miRNA, cell differentiation, miRSNPs