Suppression of miR-628-3p and miR-641 is involved in rifampin-mediated CYP3A4 induction in HepaRG cells. (January 2017)

• Record Type: Journal Article
• Authors: Yan, Liang; Liu, Jingyang; Zhao, Yunlong; Nie, Yali; Ma, Xiaochao; Kan, Quancheng; Zhang, Lirong
• Is Part Of: Pharmacogenomics. Volume 18:Number 1(2017)
• Page Start: 57
• Page End: 64
• Publication Date: 2017-01
• Subjects: CYP3A4 -- induction -- miRNA -- post-transcriptional regulation -- rifampin; Pharmacogenomics -- Periodicals; 615.1
• DOI: 10.2217/pgs-2016-0088
• Languages: English
• ISSNs: 1462-2416

Abstract

Aim: This study aimed to explore the role of miRNAs in rifampin-mediated induction of CYP3A4 in HepaRG cells.Materials & methods: 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.Results: 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.Conclusion: miR-628-3p and miR-641 could directly target CYP3A4 and are negatively regulated in CYP3A4 induction by rifampin.