Restoring the epigenetically silenced PCK2 suppresses renal cell carcinoma progression and increases sensitivity to sunitinib by promoting endoplasmic reticulum stress.
Theranostics
; 10(25): 11444-11461, 2020.
Article
em En
| MEDLINE
| ID: mdl-33052225
ABSTRACT
Rationale Tumors have significant abnormalities in various biological properties. In renal cell carcinoma (RCC), metabolic abnormalities are characteristic biological dysfunction that cannot be ignored. Despite this, many aspects of this dysfunction have not been fully explained. The purpose of this study was to reveal a new mechanism of metabolic and energy-related biological abnormalities in RCC. Methods:
Molecular screening and bioinformatics analysis were performed in RCC based on data from The Cancer Genome Atlas (TCGA) database. Regulated pathways were investigated by qRT-PCR, immunoblot analysis and immunohistochemistry. A series of functional analyses was performed in cell lines and xenograft models.Results:
By screening the biological abnormality core dataset-mitochondria-related dataset and the metabolic abnormality core dataset-energy metabolism-related dataset in public RCC databases, PCK2 was found to be differentially expressed in RCC compared with normal tissue. Further analysis by the TCGA database showed that PCK2 was significantly downregulated in RCC and predicted a poor prognosis. Through additional studies, it was found that a low expression of PCK2 in RCC was caused by methylation of its promoter region. Restoration of PCK2 expression in RCC cells repressed tumor progression and increased their sensitivity to sunitinib. Finally, mechanistic investigations indicated that PCK2 mediated the above processes by promoting endoplasmic reticulum stress.Conclusions:
Collectively, our results identify a specific mechanism by which PCK2 suppresses the progression of renal cell carcinoma (RCC) and increases sensitivity to sunitinib by promoting endoplasmic reticulum stress. This finding provides a new biomarker for RCC as well as novel targets and strategies for the treatment of RCC.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
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Tipos_de_cancer
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Outros_tipos
Base de dados:
MEDLINE
Assunto principal:
Carcinoma de Células Renais
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Resistencia a Medicamentos Antineoplásicos
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Fosfoenolpiruvato Carboxiquinase (ATP)
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Sunitinibe
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Neoplasias Renais
Tipo de estudo:
Diagnostic_studies
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Prognostic_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
Revista:
Theranostics
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China