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

This study aimed to identify novel miRNAs (miRs) as regulators of gene expression and to evaluate them as potential risk factors for the development of liver fibrosis/cirrhosis. 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. and miRNA expression were analyzed in cirrhotic patients and a mouse model of alcoholic liver fibrosis. 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. In conclusion, we identified two novel miRNAs capable to repress UGT1A expression and . 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.

PMID: 33432840