Super-enhancer-driven lncRNA-DAW promotes liver cancer cell proliferation through activation of Wnt/β-catenin pathway

Aberrant expression of long non-coding RNAs (lncRNAs) has been reported in multiple cancers. However, the underlying mechanisms mediated by super-enhancers remain elusive. Here we sought to define the role of a novel lncRNA termed lncRNA-DAW in tumorigenesis. Our results revealed that lncRNA-DAW was...

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Autores principales:	Weicheng Liang, Chuanjian Shi, Weilong Hong, Panlong Li, Xue Zhou, Weiming Fu, Lizhu Lin, Jinfang Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	cell growth lncRNA super-enhancer Wnt/β-catenin pathway liver cancer Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/853ac58ab0e4400bb591a305f25bf75f
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spelling	oai:doaj.org-article:853ac58ab0e4400bb591a305f25bf75f2021-11-22T04:23:42ZSuper-enhancer-driven lncRNA-DAW promotes liver cancer cell proliferation through activation of Wnt/β-catenin pathway2162-253110.1016/j.omtn.2021.10.028https://doaj.org/article/853ac58ab0e4400bb591a305f25bf75f2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2162253121002717https://doaj.org/toc/2162-2531Aberrant expression of long non-coding RNAs (lncRNAs) has been reported in multiple cancers. However, the underlying mechanisms mediated by super-enhancers remain elusive. Here we sought to define the role of a novel lncRNA termed lncRNA-DAW in tumorigenesis. Our results revealed that lncRNA-DAW was driven by a liver-specific super-enhancer and transcriptionally activated by HNF4G, leading to frequent elevation in hepatocellular carcinoma (HCC) specimens. Ectopic expression of lncRNA-DAW promoted both in vivo and in vitro tumor growth. By using RNA sequencing, Wnt2 was screened out as a downstream effector of lncRNA-DAW. We next found that lncRNA-DAW physically interacted with EZH2, a negative regulator of Wnt2. This interplay subsequently potentiated CDK1-EZH2 interaction, leading to the phosphorylation and ubiquitination of EZH2. The lncRNA-DAW-mediated EZH2 degradation facilitated the de-repression of Wnt2 transcription, which eventually activated the Wnt/β-catenin pathway. Furthermore, we verified that Wnt2 potentiated in vitro and in vivo cancer cell growth by activating the Wnt/β-catenin pathway. Finally, Wnt2 amplification was confirmed as a common event in liver cancer, and the expression of lncRNA-DAW was positively correlated with Wnt2 in HCC specimens. Collectively, we are the first to identify lncRNA-DAW as a novel candidate oncogene in liver cancer, and this lncRNA may serve as a novel clinical diagnosis biomarker for liver cancer.Weicheng LiangChuanjian ShiWeilong HongPanlong LiXue ZhouWeiming FuLizhu LinJinfang ZhangElsevierarticlecell growthlncRNAsuper-enhancerWnt/β-catenin pathwayliver cancerTherapeutics. PharmacologyRM1-950ENMolecular Therapy: Nucleic Acids, Vol 26, Iss , Pp 1351-1363 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cell growth lncRNA super-enhancer Wnt/β-catenin pathway liver cancer Therapeutics. Pharmacology RM1-950
spellingShingle	cell growth lncRNA super-enhancer Wnt/β-catenin pathway liver cancer Therapeutics. Pharmacology RM1-950 Weicheng Liang Chuanjian Shi Weilong Hong Panlong Li Xue Zhou Weiming Fu Lizhu Lin Jinfang Zhang Super-enhancer-driven lncRNA-DAW promotes liver cancer cell proliferation through activation of Wnt/β-catenin pathway
description	Aberrant expression of long non-coding RNAs (lncRNAs) has been reported in multiple cancers. However, the underlying mechanisms mediated by super-enhancers remain elusive. Here we sought to define the role of a novel lncRNA termed lncRNA-DAW in tumorigenesis. Our results revealed that lncRNA-DAW was driven by a liver-specific super-enhancer and transcriptionally activated by HNF4G, leading to frequent elevation in hepatocellular carcinoma (HCC) specimens. Ectopic expression of lncRNA-DAW promoted both in vivo and in vitro tumor growth. By using RNA sequencing, Wnt2 was screened out as a downstream effector of lncRNA-DAW. We next found that lncRNA-DAW physically interacted with EZH2, a negative regulator of Wnt2. This interplay subsequently potentiated CDK1-EZH2 interaction, leading to the phosphorylation and ubiquitination of EZH2. The lncRNA-DAW-mediated EZH2 degradation facilitated the de-repression of Wnt2 transcription, which eventually activated the Wnt/β-catenin pathway. Furthermore, we verified that Wnt2 potentiated in vitro and in vivo cancer cell growth by activating the Wnt/β-catenin pathway. Finally, Wnt2 amplification was confirmed as a common event in liver cancer, and the expression of lncRNA-DAW was positively correlated with Wnt2 in HCC specimens. Collectively, we are the first to identify lncRNA-DAW as a novel candidate oncogene in liver cancer, and this lncRNA may serve as a novel clinical diagnosis biomarker for liver cancer.
format	article
author	Weicheng Liang Chuanjian Shi Weilong Hong Panlong Li Xue Zhou Weiming Fu Lizhu Lin Jinfang Zhang
author_facet	Weicheng Liang Chuanjian Shi Weilong Hong Panlong Li Xue Zhou Weiming Fu Lizhu Lin Jinfang Zhang
author_sort	Weicheng Liang
title	Super-enhancer-driven lncRNA-DAW promotes liver cancer cell proliferation through activation of Wnt/β-catenin pathway
title_short	Super-enhancer-driven lncRNA-DAW promotes liver cancer cell proliferation through activation of Wnt/β-catenin pathway
title_full	Super-enhancer-driven lncRNA-DAW promotes liver cancer cell proliferation through activation of Wnt/β-catenin pathway
title_fullStr	Super-enhancer-driven lncRNA-DAW promotes liver cancer cell proliferation through activation of Wnt/β-catenin pathway
title_full_unstemmed	Super-enhancer-driven lncRNA-DAW promotes liver cancer cell proliferation through activation of Wnt/β-catenin pathway
title_sort	super-enhancer-driven lncrna-daw promotes liver cancer cell proliferation through activation of wnt/β-catenin pathway
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/853ac58ab0e4400bb591a305f25bf75f
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_version_	1718418233121308672

Super-enhancer-driven lncRNA-DAW promotes liver cancer cell proliferation through activation of Wnt/β-catenin pathway

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