CircPLEKHM3 acts as a tumor suppressor through regulation of the miR-9/BRCA1/DNAJB6/KLF4/AKT1 axis in ovarian cancer.
Mol Cancer
; 18(1): 144, 2019 10 17.
Article
em En
| MEDLINE
| ID: mdl-31623606
ABSTRACT
BACKGROUND:
Emerging evidence has shown that circular RNAs (circRNAs) play essential roles in cancer biology and are potential biomarkers and targets for cancer therapy. However, the expression and function of circRNAs in ovarian carcinogenesis and its progression remain elusive.METHODS:
RNA sequencing was performed to reveal circRNA expression profiles in ovarian cancerous and normal tissues. Single-molecule RNA in-situ hybridization was used to quantify circPLEKHM3 expression in tumor tissues. Cell-based in-vitro and in-vivo assays were subsequently conducted to support the clinical findings.RESULTS:
CircPLEKHM3 was identified as one of the most significantly down-regulated circRNAs in ovarian cancer tissues compared with normal tissues. Its expression was further decreased in peritoneal metastatic ovarian carcinomas compared to primary ovarian carcinomas. Patients with lower circPLEKHM3 tend to have a worse prognosis. Functionally, circPLEKHM3 overexpression inhibited cell growth, migration and epithelial-mesenchymal transition, whereas its knockdown exerted an opposite role. Further analyses showed that circPLEKHM3 sponged miR-9 to regulate the endogenous expression of BRCA1, DNAJB6 and KLF4, and consequently inactivate AKT1 signaling. In addition, AKT inhibitor MK-2206 could block the tumor-promoting effect of circPLEKHM3 depletion, and potentiate Taxol-induced growth inhibition of ovarian cancer cells.CONCLUSIONS:
Our findings demonstrated that circPLEKHM3 functions as a tumor suppressor in ovarian cancer cells by targeting the miR-9/BRCA1/DNAJB6/KLF4/AKT1 axis and may be used as a prognostic indicator and therapeutic target in ovarian cancer patients. The new strategy for treating ovarian cancer by a combination therapy of Taxol with MK-2206 is worth further investigation, especially in ovarian cancer patients with loss of circPLEKHM3 expression.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
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Genes Supressores de Tumor
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Chaperonas Moleculares
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Proteína BRCA1
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MicroRNAs
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Proteínas Proto-Oncogênicas c-akt
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Proteínas de Choque Térmico HSP40
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Proteínas Ligadas a Lipídeos
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RNA Circular
/
Proteínas do Tecido Nervoso
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Mol Cancer
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China