Low PDE4A expression promoted the progression of ovarian cancer by inducing Snail nuclear translocation.
Exp Cell Res
; 439(2): 114100, 2024 Jun 15.
Article
em En
| MEDLINE
| ID: mdl-38797258
ABSTRACT
Widespread metastasis is the primary reason for the high mortality associated with ovarian cancer (OC), and effective targeted therapy for tumor aggressiveness is still insufficient in clinical practice. Therefore, it is urgent to find new targets to improve prognosis of patients. PDE4A is a cyclic nucleotide phosphodiesterase that plays a crucial role in the occurrence and development in various malignancies. Our study firstly reported the function of PDE4A in OC. Expression of PDE4A was validated through bioinformatics analysis, RT-qPCR, Western blot, and immunohistochemistry. Additionally, its impact on cell growth and motility was assessed via in vitro and in vivo experiments. PDE4A was downregulated in OC tissues compared with normal tissues and low PDE4A expression was correlated with poor clinical outcomes in OC patients. The knockdown of PDE4A significantly promoted the proliferation, migration and invasion of OC cells while overexpression of PDE4A resulted in the opposite effect. Furthermore, smaller and fewer tumor metastatic foci were observed in mice bearing PDE4A-overexpressing OVCAR3 cells. Mechanistically, downregulation of PDE4A expression can induce epithelial-mesenchymal transition (EMT) and nuclear translocation of Snail, which suggests that PDE4A plays a pivotal role in suppressing OC progression. Notably, Rolipram, the PDE4 inhibitor, mirrored the effects observed with PDE4A deletion. In summary, the downregulation of PDE4A appears to facilitate OC progression by modulating the Snail/EMT pathway, underscoring the potential of PDE4A as a therapeutic target against ovarian cancer metastasis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
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Regulação Neoplásica da Expressão Gênica
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Movimento Celular
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Proliferação de Células
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Nucleotídeo Cíclico Fosfodiesterase do Tipo 4
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Transição Epitelial-Mesenquimal
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Fatores de Transcrição da Família Snail
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Exp Cell Res
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Exp. cell. res
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Experimental cell research
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China