Age-Related Changes in MicroRNA Expression and Pharmacogenes in Human Liver.
Clin Pharmacol Ther
; 98(2): 205-15, 2015 Aug.
Article
en En
| MEDLINE
| ID: mdl-25968989
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Farmacogenética
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Envejecimiento
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MicroARNs
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Hígado
Tipo de estudio:
Prognostic_studies
Límite:
Adolescent
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Adult
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Aged
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Aged80
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Child
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Child, preschool
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Humans
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Infant
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Middle aged
Idioma:
En
Revista:
Clin Pharmacol Ther
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos