MicroRNA expression is differentially altered by xenobiotic drugs in different human cell lines

Alice C. Rodrigues, Xin Li, Laura Radecki, Yu Zhuo Pan, Jerrold C. Winter, Min Huang, Aiming Yu

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Several noncoding microRNAs (miR or miRNA) have been shown to regulate the expression of drug-metabolizing enzymes and transporters. Xenobiotic drug-induced changes in enzyme and transporter expression may be associated with the alteration of miRNA expression. Therefore, this study investigated the impact of 19 xenobiotic drugs (e.g. dexamethasone, vinblastine, bilobalide and cocaine) on the expression of ten miRNAs (miR-18a, -27a, -27b, -124a, -148a, -324-3p, -328, -451, -519c and -1291) in MCF-7, Caco-2, SH-SY5Y and BE(2)-M17 cell systems. The data revealed that miRNAs were differentially expressed in human cell lines and the change in miRNA expression was dependent on the drug, as well as the type of cells investigated. Notably, treatment with bilobalide led to a 10-fold increase of miR-27a and a 2-fold decrease of miR-148a in Caco-2 cells, but no change of miR-27a and a 2-fold increase of miR-148a in MCF-7 cells. Neuronal miR-124a was generally down-regulated by psychoactive drugs (e.g. cocaine, methadone and fluoxetine) in BE(2)-M17 and SH-SY5Y cells. Dexamethasone and vinblastine, inducers of drug-metabolizing enzymes and transporters, suppressed the expression of miR-27b, -148a and -451 that down-regulate the enzymes and transporters. These findings should provide increased understanding of the altered gene expression underlying drug disposition, multidrug resistance, drug-drug interactions and neuroplasticity.

Original languageEnglish (US)
Pages (from-to)355-367
Number of pages13
JournalBiopharmaceutics and Drug Disposition
Volume32
Issue number6
DOIs
StatePublished - Sep 2011
Externally publishedYes

Fingerprint

Xenobiotics
MicroRNAs
Cell Line
Pharmaceutical Preparations
Vinblastine
Enzymes
Cocaine
Dexamethasone
Neuronal Plasticity
Caco-2 Cells
Fluoxetine
Psychotropic Drugs
Methadone
MCF-7 Cells
Multiple Drug Resistance
Drug Interactions
Down-Regulation
Gene Expression

Keywords

  • drug disposition
  • metabolism
  • miRNA
  • regulation
  • xenobiotic

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmaceutical Science
  • Pharmacology

Cite this

MicroRNA expression is differentially altered by xenobiotic drugs in different human cell lines. / Rodrigues, Alice C.; Li, Xin; Radecki, Laura; Pan, Yu Zhuo; Winter, Jerrold C.; Huang, Min; Yu, Aiming.

In: Biopharmaceutics and Drug Disposition, Vol. 32, No. 6, 09.2011, p. 355-367.

Research output: Contribution to journalArticle

Rodrigues, Alice C. ; Li, Xin ; Radecki, Laura ; Pan, Yu Zhuo ; Winter, Jerrold C. ; Huang, Min ; Yu, Aiming. / MicroRNA expression is differentially altered by xenobiotic drugs in different human cell lines. In: Biopharmaceutics and Drug Disposition. 2011 ; Vol. 32, No. 6. pp. 355-367.
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