SIRT3 promotes the invasion and metastasis of cervical cancer cells by regulating fatty acid synthase.
Mol Cell Biochem
; 464(1-2): 11-20, 2020 Jan.
Article
em En
| MEDLINE
| ID: mdl-31677030
ABSTRACT
Sirtuin 3 (SIRT3) modulates mitochondria-localized processes and is implicated in the metabolic reprogramming of cancer cells, especially fatty acid (FA) synthesis. However, the relationship between SIRT3 and aberrant lipid synthesis in cervical cancer remains unclear. Here, we investigated the clinical relevance of SIRT3 expression in cervical squamous cell carcinoma (CSCC), cervical intraepithelial neoplasia (CIN), and normal tissues. To analyze the role of SIRT3 in CCSC in vitro, endogenous SIRT3 levels were up- and down-regulated in SiHa and C33a cells, respectively, via lentiviral-based transfection. Levels were quantified using qRT-PCR. Acetylation levels for acetyl-coA carboxylase (ACC1) were measured with the anti-acetyllysine antibody. Knockdown of SIRT3 reduced levels of cellular lipid content in cells. To investigate the role of SIRT3 in cell proliferation, nude mice were xenografted with SIRT3-overexpressing or SIRT3-knockdown CCSC cells. Overall, the results demonstrate that SIRT3 significantly contributed to the reprogramming of FA synthesis in CCSC by up-regulating ACC1 to promote de novo lipogenesis by SIRT3 deacetylation. Moreover, the findings show that the SIRT3-mediated regulation of FA synthesis played a critical role in the proliferation and metastasis of CCSC cells, suggesting that SIRT3 has therapeutic potential in CCSC treatment.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Carcinoma de Células Escamosas
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Neoplasias do Colo do Útero
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Ácido Graxo Sintase Tipo I
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Sirtuína 3
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Proteínas de Neoplasias
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Mol Cell Biochem
Ano de publicação:
2020
Tipo de documento:
Article