Regulation of drug metabolism and toxicity by multiple factors of genetics, epigenetics, lncRNAs, gut microbiota, and diseases: a meeting report of the 21st International Symposium on Microsomes and Drug Oxidations (MDO)

Abstract

Variations in drug metabolism may alter drug efficacy and cause toxicity; better understanding of the mechanisms and risks shall help to practice precision medicine. At the 21st International Symposium on Microsomes and Drug Oxidations held in Davis, California, USA, in October 2–6, 2016, a number of speakers reported some new findings and ongoing studies on the regulation mechanisms behind variable drug metabolism and toxicity, and discussed potential implications to personalized medications. A considerably insightful overview was provided on genetic and epigenetic regulation of gene expression involved in drug absorption, distribution, metabolism, and excretion (ADME) and drug response. Altered drug metabolism and disposition as well as molecular mechanisms among diseased and special populations were presented. In addition, the roles of gut microbiota in drug metabolism and toxicology as well as long non-coding RNAs in liver functions and diseases were discussed. These findings may offer new insights into improved understanding of ADME regulatory mechanisms and advance drug metabolism research.

Bioengineered miR-27b-3p and miR-328-3p modulate drug metabolism and disposition via the regulation of target ADME gene expression

“…. Bioinformatics and experimental studies suggest that miRNAs, a large class of genome derived, short noncoding RNA (ncRNA) molecules participate in the regulation of ADME gene expression 7 . MiRNAs are capable of inducing translation suppression and/or mRNA cleavage of target genes via imperfect complementary Watson—Crick base pairings with targeted elements that are usually located within the 3′-untranslated regions (3′-UTRs) of target transcripts 8.…”

“…Many miRNAs have been shown to modulate the expression of specific ADME genes (see recent reviews 7. , 11.…”

The HNF1α-Regulated LncRNA HNF1α-AS1 Is Involved in the Regulation of Cytochrome P450 Expression in Human Liver Tissues and Huh7 Cells

“…Significant interindividual variability in P450-mediated drug metabolism leads to various responses to drugs in clinical practice (Zanger and Schwab, 2013). Factors contributing to changes in P450 expression and function account for the interindividual variability in P450-mediated drug metabolism, including genetic, epigenetic, physiologic, pathologic, and environmental factors (Zhou et al, 2009;Zanger et al, 2014;Tracy et al, 2016;Yu et al, 2017). Uncovering the molecular mechanisms in the regulation of P450 expression would therefore be beneficial to making therapies more effective and drugs safer.…”

Arenobufagin is a novel isoform-specific probe for sensing human sulfotransferase 2A1

“…Considering the role of SULT2A1, it has been received increasing attention to investigate the regulation of SULT2A1 expression and its activity. The current results indicate that the expression of SULT2A1 could be regulated by various nuclear receptor including farnesoid X receptor, constitutive androstane receptor, and pregnane X receptor 11 , 12 , resulting in activity variation of SULT2A1 among organs and species 13 , 14 . Moreover, the inhibitory effects of small molecules derived from natural products, environmental contaminants and drugs on SULT2A1 activities are frequently reported 15 , 16 , 17 .…”