Age-related changes in MicroRNA expression and pharmacogenes in human liver

K. S. Burgess, S. Philips, Eric Benson, Zeruesenay Desta, A. Gaedigk, R. Gaedigk, M. W. Segar, Yunlong Liu, Todd Skaar

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)205-215
Number of pages11
JournalClinical Pharmacology and Therapeutics
Volume98
Issue number2
DOIs
StatePublished - Aug 1 2015

Fingerprint

MicroRNAs
Liver
Pediatrics
Pharmaceutical Preparations
RNA Sequence Analysis
Gene Expression
Messenger RNA
Cytochrome P-450 CYP1A1
Regulator Genes
Fetus
Down-Regulation

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Age-related changes in MicroRNA expression and pharmacogenes in human liver. / Burgess, K. S.; Philips, S.; Benson, Eric; Desta, Zeruesenay; Gaedigk, A.; Gaedigk, R.; Segar, M. W.; Liu, Yunlong; Skaar, Todd.

In: Clinical Pharmacology and Therapeutics, Vol. 98, No. 2, 01.08.2015, p. 205-215.

Research output: Contribution to journalArticle

Burgess, K. S. ; Philips, S. ; Benson, Eric ; Desta, Zeruesenay ; Gaedigk, A. ; Gaedigk, R. ; Segar, M. W. ; Liu, Yunlong ; Skaar, Todd. / Age-related changes in MicroRNA expression and pharmacogenes in human liver. In: Clinical Pharmacology and Therapeutics. 2015 ; Vol. 98, No. 2. pp. 205-215.
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