ATP citrate lyase promotes the progression of hepatocellular carcinoma by activating the REGγ-proteasome pathway.
ATP citrate lyase
H3K27ac
REGγ
hepatocellular carcinoma
proteasome pathway
Journal
Molecular carcinogenesis
ISSN: 1098-2744
Titre abrégé: Mol Carcinog
Pays: United States
ID NLM: 8811105
Informations de publication
Date de publication:
18 Jun 2024
18 Jun 2024
Historique:
revised:
23
05
2024
received:
20
01
2024
accepted:
04
06
2024
medline:
18
6
2024
pubmed:
18
6
2024
entrez:
18
6
2024
Statut:
aheadofprint
Résumé
The search for novel tumor biomarkers and targets is of significant importance for the early clinical diagnosis and treatment of Hepatocellular Carcinoma (HCC). The mechanisms by which ATP citrate lyase (ACLY) promotes HCC progression remain unclear, and the connection between ACLY and REGγ has not been reported in the literature. In vitro, we will perform overexpression/knockdown of ACLY or overexpression/knockdown of REGγ to investigate the impact of ACLY on HCC cells and its underlying mechanisms. In vivo, we will establish mouse tumor models with overexpression/knockdown of ACLY or overexpression/knockdown of REGγ to study the effect of ACLY on mouse tumors and its mechanisms. Firstly, ACLY overexpression upregulated REGγ expression and activated the REGγ-proteasome pathway, leading to changes in the expression of downstream signaling pathway proteins. This promoted HCC cell proliferation, invasion, and migration in vitro, as well as tumor growth and metastasis in vivo. Secondly, ACLY overexpression increased acetyl-CoA production, upregulated the acetylation level of the REGγ promoter region histone H3K27ac, and subsequently induced REGγ expression. Lastly, enhanced acetylation of the REGγ promoter region histone H3K27ac resulted in upregulated REGγ expression, activation of the REGγ-proteasome pathway, changes in downstream signaling pathway protein expression, and promotion of HCC cell proliferation, invasion, and migration in vitro, as well as tumor growth and metastasis in vivo. Conversely, REGγ knockdown reversed these effects. ACLY and REGγ may serve as potential biomarkers and clinical therapeutic targets for HCC.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Wenzhou Science and Technology Project
ID : Y20210172
Organisme : Province Key Surgery Projects (Zhejiang High-Tech 2008-255, Zhejiang High-Tech 2012-80 and Zhejiang High-Tech 2016-169)
Informations de copyright
© 2024 Wiley Periodicals LLC.
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