BAG3 upregulates Mcl-1 through downregulation of miR-29b to induce anticancer drug resistance in ovarian cancer.
Gynecol Oncol
; 134(3): 615-23, 2014 Sep.
Article
em En
| MEDLINE
| ID: mdl-24992675
ABSTRACT
OBJECTIVE:
Ovarian cancer is the leading cause of death from gynecologic cancer, reflecting its often late diagnosis and its chemoresistance. We identified a set of microRNAs whose expression is altered upon BAG3 knockdown. Our primary objective was to examine the relationships between BAG3, miR-29b and Mcl-1, an antiapoptotic Bcl-2 family protein, in ovarian cancer cells.METHODS:
Ovarian cancer cells were cultured and their responsiveness to paclitaxel was tested. Microarray analysis was performed to identify microRNAs differentially expressed in ES2 BAG3 knockdown ovarian cancer cells and their control cells. Primary ovarian cancer tissues were obtained from 56 patients operated on for ovarian cancer. The patients' clinical and pathological data were obtained from their medical records.RESULTS:
BAG3 knockdown increased the chemosensitivity to paclitaxel of ES2 ovarian clear cell carcinoma cells to a greater degree than AMOC2 serous adenocarcinoma cells. qRT-PCR analysis showed that miR-29b expression was significantly upregulated in primary cancer tissue expressing low levels of BAG3, as compared to tissue expressing high levels. Moreover, levels of miR-29b correlated significantly with progression-free survival. Upregulation of miR-29b also reduced levels of Mcl-1 and sensitized ES2 cells to low-dose paclitaxel.CONCLUSIONS:
BAG3 knockdown appears to downregulate expression of Mcl-1 through upregulation of miR-29b, thereby increasing the chemosensitivity of ovarian clear cell carcinoma cells. This suggests that BAG3 is a key determinant of the responsiveness of ovarian cancer cells, especially clear cell carcinoma, to paclitaxel and that BAG3 may be a useful therapeutic target for the treatment of ovarian cancer.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
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Regulação para Baixo
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Regulação para Cima
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Paclitaxel
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Adenocarcinoma de Células Claras
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Resistencia a Medicamentos Antineoplásicos
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MicroRNAs
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Proteínas Adaptadoras de Transdução de Sinal
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Proteínas Reguladoras de Apoptose
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Proteína de Sequência 1 de Leucemia de Células Mieloides
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Aged
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Female
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article