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Let-7g induces granulosa cell apoptosis by targeting MAP3K1 in the porcine ovary.
- Source :
-
International Journal of Biochemistry & Cell Biology . Nov2015, Vol. 68, p148-157. 10p. - Publication Year :
- 2015
-
Abstract
- Follicular atresia mainly results from apoptosis of granulosa cells (GCs). Our previous microRNA array data indicated that the miRNA let-7g level increases significantly during porcine ovary follicular atresia. It is uncertain if GCs apoptosis is mediated by microRNA let-7g. In this study, the expression levels of the apoptosis-associated genes CASP3 , BAX and BIM were significantly upregulated when let-7g mimic was transfected into porcine GCs, and the anti-apoptotic genes BCL-2 and MCL-1 were significantly downregulated. The apoptosis rate was measured by flow cytometry, and our results indicated that let-7g significantly enhanced GCs apoptosis. In further studies, we found that overexpression of let-7g induced the expression of FoxO1 in GCs and led to nuclear accumulation of dephosphorylated FoxO1. In addition, the effect of let-7g on FoxO1 expression and dephosphorylation resulted from repression of the expression of the MAP3K1 gene in porcine GCs. The site on MAP3K1 mRNA targeted by let-7g was confirmed by luciferase reporter assay. The anti-apoptotic effect of MAP3K1 was validated by silencing MAP3K1 using small interfering RNA technology. In conclusion, our data indicate that let-7g induces porcine GCs apoptosis by inhibiting the MAP3K1 gene, which promotes FoxO1 expression and dephosphorylation with nuclear accumulation. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 13572725
- Volume :
- 68
- Database :
- Academic Search Index
- Journal :
- International Journal of Biochemistry & Cell Biology
- Publication Type :
- Academic Journal
- Accession number :
- 110632289
- Full Text :
- https://doi.org/10.1016/j.biocel.2015.08.011