Inflammation-Induced Long Intergenic Noncoding RNA (LINC00665) Increases Malignancy Through Activating the Double-Stranded RNA-Activated Protein Kinase/Nuclear Factor Kappa B Pathway in Hepatocellular Carcinoma.
Hepatology
; 72(5): 1666-1681, 2020 11.
Article
em En
| MEDLINE
| ID: mdl-32083756
ABSTRACT
BACKGROUND AND AIMS:
The nuclear factor kappa B (NF-κB) signaling pathway is important for linking inflammation and tumorigenesis. Here, we characterized an NF-κB signaling activation-induced long intergenic noncoding (LINC) RNA in hepatocellular carcinoma (HCC), LINC00665, that contributes to the enhanced cell proliferation of HCC cells both in vitro and in vivo. APPROACH ANDRESULTS:
LINC00665 physically interacts with the double-stranded RNA (dsRNA)-activated protein kinase (PKR), enhances its activation, and maintains its protein stability by blocking ubiquitin/proteasome-dependent degradation, resulting in a positive feedback regulation of NF-κB signaling in HCC cells. Notably, patients with HCC and higher LINC00665 have poorer outcomes in the clinic.CONCLUSIONS:
Our findings indicate that LINC00665 is involved in the NF-κB signaling activation in HCC cells and that the inflammatory LINC00665/PKR/NF-κB loop plays important oncogenic roles in hepatic cancer progression and may be a potential therapeutic target.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Biomarcadores Tumorais
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Carcinoma Hepatocelular
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EIF-2 Quinase
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RNA Longo não Codificante
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Neoplasias Hepáticas
Tipo de estudo:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article