Age-Related Changes in MicroRNA Expression and Pharmacogenes in Human Liver
K S Burgess1,2, S Philips2, E A Benson2
1Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Clinical Pharmacology and Therapeutics
|May 14, 2015
Summary
MicroRNAs (miRNAs) significantly influence drug metabolism during development. This study reveals age-dependent miRNA expression changes in the liver, impacting drug disposition gene regulation from fetal to adult stages.
Area of Science:
- Pharmacogenomics
- Developmental Biology
- Molecular Biology
Background:
- Liver development involves significant changes impacting drug metabolism.
- MicroRNAs (miRNAs) are key regulators of gene expression, including those involved in drug disposition.
Purpose of the Study:
- To investigate age-dependent changes in miRNA expression in human liver tissues.
- To identify miRNAs that regulate drug disposition genes during development.
Main Methods:
- Expression profiling of 533 miRNAs in 90 human liver samples (fetal, pediatric, adult).
- Prediction and validation of miRNA-mRNA interactions.
- RNA-sequencing to analyze correlations between miRNA and mRNA expression.
Main Results:
- Significant upregulation and downregulation of numerous miRNAs observed from fetal to pediatric stages.
- Few miRNAs showed changes from pediatric to adult stages.
- Over 1,000 negative correlations found between miRNA and drug disposition/regulatory gene mRNA expression.
Conclusions:
- Age-dependent miRNA expression changes provide a mechanism for altered hepatic gene expression during development.
- These miRNAs play a crucial role in regulating drug disposition across different life stages.
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