Abstract 3089: miR-491-3p regulation of the UDP-glucuronosyltransferase (UGT) 1A gene family.

Background: The UDP-Glucuronosyltransferases (UGTs) are phase II metabolic enzymes that prime endogenous and exogenous compounds for excretion from the body. The UGTs are often found to have high inter-individual differences in expression, and this impacts patients’ response to drug therapy. Studies examining the epigenetic regulation of the UGT enzymes have not previously been performed. Recently, it has been shown that the phase I metabolic cytochrome P-450s (CYPs) are negatively regulated by microRNA (miRNA). miRNA are short, endogenous strands of RNA roughly 22-24 nucleotides in length that regulate gene expression. MiRNA specifically bind to the 3’ untranslated region (UTR) of mature messenger RNA (mRNA) and post-transcriptionally repress protein expression. Purpose: The goal of this study is to identify and evaluate miRNA regulation of UGT1A expression and whether this regulation contributes to differences in UGT1A enzymatic activity. Results: miR-491-3p was identified using the miRanda prediction program. Luciferase assays showed a significant reduction in luciferase activity with an attached UGT1A 3’UTR in the presence of miR-491-3p mimic (P Citation Format: Douglas F. Dluzen, Anna Salzberg, Dongxiao Sun, Nathan Jones, Ryan Bushey`, Philip Lazarus. miR-491-3p regulation of the UDP-glucuronosyltransferase (UGT) 1A gene family. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3089. doi:10.1158/1538-7445.AM2013-3089