MicroRNA146a5p enhances cisplatininduced apoptosis in ovarian cancer cells by targeting multiple antiapoptotic genes.
Int J Oncol
; 51(1): 327-335, 2017 Jul.
Article
em En
| MEDLINE
| ID: mdl-28560455
ABSTRACT
MicroRNAs play a crucial role in gene expression regulation in various types of cancers. Previous studies show the expression level of miR146a5p is downregulated in epithelial ovarian cancer. Further investigations suggest this downregulation is responsible for apoptosis resistance in ovarian cancer cells. However, the mechanism of how miR146a5p promotes apoptosis remains unclear. In this study, the role of miR146a5p in cisplatininduced apoptosis of ovarian cancer cells was assessed by DAPI staining, MTT assays, and monitoring expression of XIAP, BCL2L2, BIRC2 and BIRC5 through a dualluciferase assay. Our results show that miR146a5p can regulate three important antiapoptotic genes including XIAP, BCL2L2 and BIRC5 via their 3'UTRs. Not only can overexpression of miR146a5p downregulate the expression of XIAP in SKOV3 cells, but it also lowers the IC50 values of cisplatin in OVCAR3 and SKOV3 cells and enhances the susceptibility of OVCAR3, SKOV3 and primary ovarian cancer cells to cisplatininduced apoptosis. The effect of XIAP rescuing cisplatininduced apoptosis accelerated by miR146a5p further supports our conclusion. Our results suggest that the regulation of three antiapoptotic genes by miR1465p enhances the therapeutic effects of cisplatin.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
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Cisplatino
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MicroRNAs
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Ubiquitina-Proteína Ligases
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Proteínas Reguladoras de Apoptose
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Proteínas Inibidoras de Apoptose
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Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X
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Antineoplásicos
Limite:
Female
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Humans
Idioma:
En
Revista:
Int J Oncol
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2017
Tipo de documento:
Article