Regulation of microRNA expression by rifampin in human hepatocytes

Anuradha Ramamoorthy, Yunlong Liu, Santosh Philips, Zeruesenay Desta, Hai Lin, Chirayu Goswami, Andrea Gaedigk, Lang Li, David A. Flockhart, Todd C. Skaar

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Rifampin causes drug interactions by altering hepatic drug metabolism. Because microRNAs (miRNAs) have been shown to regulate genes involved in drug metabolism, we determined the effect of rifampin on the expression of hepatic miRNAs. Primary human hepatocytes from seven subjects were treated with rifampin, and the expression of miRNA and cytochrome P450 (P450) mRNAs was measured by TaqMan assays and RNA-seq, respectively. Rifampin induced the expression of 10 clinically important and 13 additional P450 genes and repressed the expression of 9 other P450 genes (P < 0.05). Rifampin induced the expression of 33 miRNAs and repressed the expression of 35 miRNAs (P < 0.05). Several of these changes were highly negatively correlated with the rifampin-induced changes in the expression of their predicted target P450 mRNAs, supporting the possibility of miRNA-induced regulation of P450 mRNA expression. In addition, several other miRNA changes were positively correlated with the changes in P450 mRNA expression, suggesting similar regulatory mechanisms. Despite the interindividual variability in the rifampin effects on miRNA expression, principal components analysis clearly separated the rifampin-treated samples from the controls. In conclusion, rifampin treatment alters miRNA expression patterns in human hepatocytes, and some of the changes were correlated with the rifampin-induced changes in expression of the P450 mRNAs they are predicted to target.

Original languageEnglish (US)
Pages (from-to)1763-1768
Number of pages6
JournalDrug Metabolism and Disposition
Volume41
Issue number10
DOIs
StatePublished - Oct 1 2013

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Rifampin
MicroRNAs
Hepatocytes
Messenger RNA
Liver
Principal Component Analysis
Drug Interactions
Pharmaceutical Preparations
Cytochrome P-450 Enzyme System
Genes
RNA
Gene Expression

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Cite this

Regulation of microRNA expression by rifampin in human hepatocytes. / Ramamoorthy, Anuradha; Liu, Yunlong; Philips, Santosh; Desta, Zeruesenay; Lin, Hai; Goswami, Chirayu; Gaedigk, Andrea; Li, Lang; Flockhart, David A.; Skaar, Todd C.

In: Drug Metabolism and Disposition, Vol. 41, No. 10, 01.10.2013, p. 1763-1768.

Research output: Contribution to journalArticle

Ramamoorthy, A, Liu, Y, Philips, S, Desta, Z, Lin, H, Goswami, C, Gaedigk, A, Li, L, Flockhart, DA & Skaar, TC 2013, 'Regulation of microRNA expression by rifampin in human hepatocytes', Drug Metabolism and Disposition, vol. 41, no. 10, pp. 1763-1768. https://doi.org/10.1124/dmd.113.052886
Ramamoorthy, Anuradha ; Liu, Yunlong ; Philips, Santosh ; Desta, Zeruesenay ; Lin, Hai ; Goswami, Chirayu ; Gaedigk, Andrea ; Li, Lang ; Flockhart, David A. ; Skaar, Todd C. / Regulation of microRNA expression by rifampin in human hepatocytes. In: Drug Metabolism and Disposition. 2013 ; Vol. 41, No. 10. pp. 1763-1768.
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