Burgess, Kimberly S.Philips, SantoshBenson, Eric A.Desta, ZeruesenayGaedigk, AndreaGaedigk, RogerSegar, Matthew W.Liu, YunlongSkaar, Todd C.2017-05-232017-05-232015-08Burgess, K. S., Philips, S., Benson, E. A., Desta, Z., Gaedigk, A., Gaedigk, R., … Skaar, T. C. (2015). Age-related changes in microRNA expression and pharmacogenes in human liver. Clinical Pharmacology and Therapeutics, 98(2), 205–215. http://doi.org/10.1002/cpt.145https://hdl.handle.net/1805/12704Developmental changes in the liver can significantly impact drug disposition. Due to the emergence of microRNAs (miRNAs) as important regulators of drug disposition gene expression, we studied age-dependent changes in miRNA expression. Expression of 533 miRNAs was measured in 90 human liver tissues (fetal, pediatric [1-17 years], and adult [28-80 years]; n = 30 each). In all, 114 miRNAs were upregulated and 72 were downregulated from fetal to pediatric, and 2 and 3, respectively, from pediatric to adult. Among the developmentally changing miRNAs, 99 miRNA-mRNA interactions were predicted or experimentally validated (e.g., hsa-miR-125b-5p-CYP1A1; hsa-miR-34a-5p-HNF4A). In human liver samples (n = 10 each), analyzed by RNA-sequencing, significant negative correlations were observed between the expression of >1,000 miRNAs and mRNAs of drug disposition and regulatory genes. Our data suggest a mechanism for the marked changes in hepatic gene expression between the fetal and pediatric developmental periods, and support a role for these age-dependent miRNAs in regulating drug disposition.en-USPublisher PolicyLiverFetusPediatricAgeDevelopmentOntogenyArticle