Long noncoding RNA NEAT1 suppresses hepatocyte proliferation in fulminant hepatic failure through increased recruitment of EZH2 to the LATS2 promoter region and promotion of H3K27me3 methylation.

Experimental & Molecular Medicine
Qiang WangYujun Zhao

Abstract

Fulminant hepatic failure (FHF) refers to the rapid development of severe acute liver injury with impaired synthetic function and encephalopathy in people with normal liver or well-compensated liver disease. This study aimed to investigate the function of long noncoding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1) on the proliferation and apoptosis of hepatocytes in FHF. Our results revealed that lncRNA NEAT1 was upregulated in cell and animal models of FHF induced by D-galactosamine (D-GalN)/lipopolysaccharide (LPS). Overexpression of lncRNA NEAT1 resulted in elevated hepatocyte apoptosis and impaired large tumor-suppressor kinase 2 (LATS2) expression and proliferation. Functional analysis revealed that knockdown of lncRNA NEAT1 inhibited hepatocyte apoptosis and induced proliferation both in vitro and in vivo. RNA immunoprecipitation and chromatin immunoprecipitation assays demonstrated that lncRNA NEAT1 recruited enhancer of zeste homolog 2 (EZH2) to the LATS2 promoter and repressed LATS2 expression. Furthermore, ectopic expression of LATS2 increased proliferation and inhibited hepatocyte apoptosis by regulating the Hippo/Yes-associated protein (YAP) signaling pathway. Taken together, our findings indicate tha...Continue Reading

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Citations

Sep 18, 2020·Epigenomics·Ning KangFrancesco Crea
Sep 3, 2020·Non-coding RNA·Shizuka Uchida, Sakari Kauppinen
Aug 4, 2020·Liver International : Official Journal of the International Association for the Study of the Liver·Fang-Tian BuJun Li
Aug 22, 2021·Cardiovascular Toxicology·Mehran AmrovaniMozhdeh Sanei

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Methods Mentioned

BETA
acetylation
electrophoresis
X-ray
immunoprecipitation
scraping
RIP
ChIP
confocal microscopy
ELISA
ubiquitination

Software Mentioned

SPSS
DNATriplex
ImageProPlus

Related Concepts

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis