Research Article

Regulation of uridine diphosphate-glucuronosyltransferase 1A expression by miRNA-214-5p and miRNA-486-3p

Stefan Paulusch

Department of Internal Medicine I, University Hospital Bonn, Bonn 53127, Germany

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Sandra Kalthoff

*Author for correspondence: Tel.: +49 2282 8719 801;

E-mail Address: Sandra.Kalthoff@ukbonn.de

https://orcid.org/0000-0002-0882-0957

Department of Internal Medicine I, University Hospital Bonn, Bonn 53127, Germany

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Steffen Landerer

Department of Internal Medicine I, University Hospital Bonn, Bonn 53127, Germany

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Christian Jansen

Department of Internal Medicine I, University Hospital Bonn, Bonn 53127, Germany

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Robert Schierwagen

Department of Internal Medicine I, University Hospital Frankfurt, Frankfurt 60590, Germany

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Sabine Klein

Department of Internal Medicine I, University Hospital Frankfurt, Frankfurt 60590, Germany

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Jonel Trebicka

Department of Internal Medicine I, University Hospital Frankfurt, Frankfurt 60590, Germany

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Christian P Strassburg

Department of Internal Medicine I, University Hospital Bonn, Bonn 53127, Germany

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Published Online:12 Jan 2021https://doi.org/10.2217/epi-2020-0244

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Abstract

Aim: This study aimed to identify novel miRNAs (miRs) as regulators of UGT1A gene expression and to evaluate them as potential risk factors for the development of liver fibrosis/cirrhosis. Materials & methods: miRNA target sites in UDP-glucuronosyltransferase 1A (UGT1A) 3′-UTR were predicted and confirmed by luciferase assays, quantitative real-time PCR and western blot using HEK293, HepG2 and Huh7 cells. UGT1A and miRNA expression were analyzed in cirrhotic patients and a mouse model of alcoholic liver fibrosis. Results: miR-214-5p and miR-486-3p overexpression reduced UGT1A mRNA, protein levels and enzyme activity in HepG2 and Huh7 cells. miR-486-3p was upregulated in cirrhotic patients and fibrotic mice livers, whereas UGT1A mRNA levels were reduced. Conclusion: In conclusion, we identified two novel miRNAs capable to repress UGT1A expression in vitro and in vivo. Furthermore, miR-486-3p may represent a potential risk factor for the development or progression of liver fibrosis/cirrhosis by means of a reduced UGT1A-mediated detoxification activity.

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Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 13, No. 4

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History

Received 8 June 2020

Accepted 8 December 2020

Published online 12 January 2021

Published in print February 2021

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Keywords

Author contributions

S Paulusch and CP Strassburg contributed in the study and experiment design. S Paulusch, S Kalthoff and S Landerer participated in the experimental work. R Schierwagen and S Klein were involved in sample collection. S Paulusch, C Jansen, R Schierwagen, S Klein, J Trebicka and CP Strassburg contributed to the data interpretation. S Paulusch, S Kalthoff, S Landerer and CP Strassburg participated in data analysis. C Jansen, R Schierwagen, S Klein and J Trebicka participated in the discussion. S Paulusch, S Kalthoff and CP Strassburg were involved in the writing of the manuscript. CP Strassburg contributed to the funcding of this study.

Acknowledgments

We thank G Hack and S Bellinghausen for their excellent technical assistance.

Financial & competing interests disclosure

Our research work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) project STR493/8-1. 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 the 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.

Data sharing statement

Data are available from the corresponding author upon request.

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