title: MicroRNA expression is differentially altered by xenobiotic drugs in different human cell lines.
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.
authors.affiliation: Department of Pharmaceutical Sciences, University at Buffalo, SUNY, Buffalo, NY 14260, USA.
authors.forename: Alice C
authors.initials: AC
authors.lastname: Rodrigues
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Laura
authors.initials: L
authors.lastname: Radecki
authors.forename: Yu-Zhuo
authors.initials: YZ
authors.lastname: Pan
authors.forename: Jerrold C
authors.initials: JC
authors.lastname: Winter
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.forename: Ai-Ming
authors.initials: AM
authors.lastname: Yu
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism / Q000494:pharmacology; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D003042:Cocaine / Q000378:metabolism / Q000494:pharmacology; D003517:Cyclopentanes / Q000378:metabolism / Q000494:pharmacology; D003907:Dexamethasone / Q000378:metabolism / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000378:metabolism / Q000494:pharmacology; D015536:Down-Regulation; D004347:Drug Interactions / Q000235:genetics / Q000502:physiology; D018432:Drug Resistance, Multiple / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D005663:Furans / Q000378:metabolism / Q000494:pharmacology; D015870:Gene Expression; D046934:Ginkgolides / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics / Q000502:physiology; D055029:Inverted Repeat Sequences / Q000187:drug effects; D035683:MicroRNAs / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D014747:Vinblastine / Q000378:metabolism / Q000494:pharmacology; D015262:Xenobiotics / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D018528:ATP-Binding Cassette Transporters; D000972:Antineoplastic Agents, Phytogenic; D003517:Cyclopentanes; D018765:Dopamine Uptake Inhibitors; D005663:Furans; D046934:Ginkgolides; D035683:MicroRNAs; D015262:Xenobiotics; D014747:Vinblastine; D003907:Dexamethasone; D003042:Cocaine; C073710:bilobalide