Abstract
This study aimed to explore the role of miRNAs in rifampin-mediated induction of CYP3A4 in HepaRG cells. Microarray was performed to determine the expression of miRNAs in rifampin-treated HepaRG cells, followed by bioinformatics and luciferase reporter gene assay to analyze miRNAs that directly target CYP3A4. Overexpression of miRNA mimics was used to study their effects on CYP3A4 induction. Forty-seven miRNAs were suppressed and 18 miRNAs were increased by rifampin (above twofold). MiR-628-3p and miR-641 repressed the 3'-UTR luciferase activity of CYP3A4. Overexpression of miR-628-3p and miR-641 showed significant decrease of CYP3A4 mRNA level as well as CYP3A4 induction by rifampin. miR-628-3p and miR-641 could directly target CYP3A4 and are negatively regulated in CYP3A4 induction by rifampin.
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