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

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.

journal_name

Epigenomics

journal_title

Epigenomics

authors

Paulusch S,Kalthoff S,Landerer S,Jansen C,Schierwagen R,Klein S,Trebicka J,Strassburg CP

doi

10.2217/epi-2020-0244

subject

Has Abstract

pub_date

2021-01-12 00:00:00

eissn

1750-1911

issn

1750-192X

pub_type

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