Novel mechanism of miRNA-365-regulated trophoblast apoptosis in recurrent miscarriage.
J Cell Mol Med
; 21(10): 2412-2425, 2017 10.
Article
em En
| MEDLINE
| ID: mdl-28393453
Clinical pregnancies increasingly end in recurrent miscarriage (RM) during the first trimester, with genetic factors shouldering the main responsibility. MicroRNAs (miRNAs) regulate gene expression in a wide array of important biological processes. We examined the potential role of dysregulated miRNAs in RM pathogenesis and trophoblast development as an approach to elucidate the molecular mechanism behind RM. miRNA profiles from clinical specimens of RM and induced abortion (IA) were compared, and several miRNAs were found to be aberrantly expressed in RM samples. Among the miRNAs, miR-365 was significantly differentially expressed in RM decidual tissues. Furthermore, our results demonstrate that miR-365 functions as an upstream regulator of MDM2/p53 expression, cell cycle progression and apoptosis in trophoblasts. Bioinformatic prediction and experimental validation assays identified SGK1 as a direct target of miR-365; consistently, its protein levels were low in decidual tissues. Additionally, functional studies revealed that SGK1 silencing elicits cell cycle arrest and apoptosis in trophoblasts and that SGK1 overexpression attenuates the effects of miR-365 on apoptosis and MDM2/p53 expression. Collectively, our data provide evidence that the up-regulation of miR-365 may contribute to RM by decreasing SGK1 expression, which suggests its potential utility as a prognostic biomarker and therapeutic target for RM.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Trofoblastos
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Aborto Habitual
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Regulação da Expressão Gênica
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Apoptose
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MicroRNAs
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Female
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Humans
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Pregnancy
Idioma:
En
Revista:
J Cell Mol Med
Ano de publicação:
2017
Tipo de documento:
Article