Hypoxia-induced microRNA-191 contributes to hepatic ischemia/reperfusion injury through the ZONAB/Cyclin D1 axis.

Cell Death and Differentiation
Wenming PanHui Wang

Abstract

Hepatic ischemia/reperfusion injury (IRI) is a common cause of morbidity and mortality in liver transplantation settings and involves severe cell death and inflammatory responses. MicroRNA-191 has recently been reported to be abnormally expressed in hepatocellular carcinoma and other liver diseases in the regulation of important cellular processes. However, little is known about its function and molecular mechanism in IRI. Here, we demonstrate that miR-191 is significantly upregulated in a cultured cell line during hypoxia/reperfusion (H/R) and in liver tissue during IRI in mice. The activation of miR-191 under hypoxic conditions is mediated by hypoxia-inducible factor-1α (HIF1α) binding to its promoter region. Global miR-191 KO mice were constructed by CRISPR/Cas9 system, and we found that miR-191 deficiency markedly reduces liver tissue damage, cell inflammatory responses and cell death in a mouse hepatic IRI model. Under the H/R condition, miR-191 overexpression promotes G0/G1 cell cycle arrest and cell apoptosis, but inhibition of miR-191 facilitates cell cycle progression and decreases cell death. Mechanistically, upon induction by hypoxia or ischemia, miR-191 suppresses expression of ZO-1-associated Y-box factor (ZONAB) a...Continue Reading

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Citations

Mar 11, 2020·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Wen-Ming PanJin-Xiang Zhang
Oct 27, 2020·Oxidative Medicine and Cellular Longevity·Wan-Li JiangSong-Ping Xie
Mar 6, 2021·Molecular Therapy. Nucleic Acids·Fengwei LiKui Wang
Apr 16, 2021·Journal of Hepatology·Oliver D TavabieUNKNOWN United States Acute Liver Failure Study Group
May 7, 2021·Journal of Cellular and Molecular Medicine·Jian ShenJianwei Pan

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Methods Mentioned

BETA
immunoprecipitation
ChIPs
PCR
genotyping
fluorescence activated cell sorting
FACS
transfection
ChIP
light microscopy

Software Mentioned

GraphPad
SPSS
GraphPad Prism
Genomatix
Image J

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