Age‐Related Changes in MicroRNA Expression and Pharmacogenes in Human Liver
Year: 2015
Type: article
Study design: Observational Study
Abstract: Developmental 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.
DOI: 10.1002/cpt.145
Language: English
Subfield: Pharmacology
Domain: Life Sciences
Open Access status: green
Funders: National Institutes of Health, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, U.S. National Library of Medicine, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1759177649, Pineal Regulation: Control of arylalkylamine N-acetyltransferase, Indiana Clinical and Translational Sciences Institute, Regulation of drug metabolizing enzymes by miRNAs, Age-related changes in microRNA expression effect on drug metabolism in human liver, G7446276365, G8604562162, G8675967096
OpenAlex ID: W1597309278