Regulation of Cytochorome P450s and Nuclear Receptors by microRNAs and its Toxicological Implications
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May 1, 2012
Tsuyoshi Yokoi, Professor, Drug Metabolism and Toxicology Laboratory, Kanazawa University
Abstract
MicroRNAs (miRNAs) regulate gene expression by targeting messenger RNAs (mRNAs) by binding to complementary regions of transcripts to repress their translation or mRNA degradation. MiRNAs are encoded by the genome, and approximately 1,500 human miRNAs have been identified so far. MiRNAs are predicted to target ~60% of human mRNAs and are expressed in all animal cells and have fundamental roles in cellular responses to xenobiotic stresses, which affect a large range of physiological processes such as development, immune responses, metabolism, tumor formation as well as toxicological outcomes. Recently, many reports concerning miRNAs related to cancer have been published, however, the miRNA research in the metabolism of xenobiotics and endobiotics and in toxicology has only recently been established. The current knowledge on the miRNA-dependent regulation of drug metabolizing enzymes and nuclear receptors and its potential toxicological implications well be presented with the following new topics; human HNF4a and miR-24/miR-34a, human PPARa and miR-21/miR-27b, human ARNT and miR-24, and plasma miRNA profiles of hepatocellular injury, cholestasis and steatosis.
