Suppression of miR-628-3p and miR-641 is Involved in Rifampin-Mediated CYP3A4 Induction in HepaRG Cells

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.

Keywords::

• CYP3A4
• induction
• miRNA
• post-transcriptional regulation
• rifampin

Supplementary data

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Financial & competing interests disclosure

This work was supported by the National Natural Science Foundation of China (grant no. 81173127, 81273581). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (grant no. 81173127, 81273581). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.