Age-Related Changes in MicroRNA Expression and Pharmacogenes in Human Liver

被引：32

作者：

Burgess, K. S. ^{[1
,2
]}

Philips, S. ^{[2
]}

Benson, E. A. ^{[2
]}

Desta, Z. ^{[2
]}

Gaedigk, A. ^{[3
,4
]}

Gaedigk, R. ^{[3
,4
]}

Segar, M. W. ^{[5
]}

Liu, Y. ^{[5
,6
]}

Skaar, T. C. ^{[2
]}

机构：

[1] Indiana Univ Sch Med, Dept Pharmacol & Toxicol, Indianapolis, IN 46202 USA

[2] Indiana Univ Sch Med, Dept Med, Div Clin Pharmacol, Indianapolis, IN 46202 USA

[3] Childrens Mercy Hosp, Div Clin Pharmacol Toxicol & Therapeut Innovat, Kansas City, MO 64108 USA

[4] Univ Missouri, Sch Med, Kansas City, MO 64108 USA

[5] Indiana Univ Sch Med, Ctr Computat Biol & Bioinformat, Indianapolis, IN 46202 USA

[6] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA

来源：

CLINICAL PHARMACOLOGY & THERAPEUTICS | 2015年 / 98卷 / 02期

关键词：

DRUG-METABOLIZING-ENZYMES; GENE-EXPRESSION; DEVELOPMENTAL EXPRESSION; PROTEIN-SYNTHESIS; MESSENGER-RNA; ONTOGENY; RIFAMPIN; DISPOSITION; SUPPRESSES; TRANSPORT;

D O I：

10.1002/cpt.145

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页码：205 / 215

页数：11

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