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Conserved miR-10 family represses proliferation and induces apoptosis in ovarian granulosa cells.
- Source :
-
Scientific reports [Sci Rep] 2017 Jan 23; Vol. 7, pp. 41304. Date of Electronic Publication: 2017 Jan 23. - Publication Year :
- 2017
-
Abstract
- Granulosa cells (GCs) are essential somatic cells in the ovary and play an important role in folliculogenesis. Brain-derived neurotropic factor (BDNF) and the TGF-β pathway have been identified as a critical hormone and signalling pathway, respectively, in GCs. In this study, we found that a conserved microRNA family that includes miR-10a and miR-10b repressed proliferation and induced apoptosis in human, mouse, and rat GCs (hGCs, mGCs and rGCs, respectively). Moreover, essential hormones and growth factors in the follicle, such as FSH, FGF9 and some ligands in the TGF-β pathway (TGFβ1, Activin A, BMP4 and BMP15), inhibited miR-10a and miR-10b expression in GCs. In contrast, the miR-10 family suppressed many key genes in the TGF-β pathway, suggesting a negative feedback loop between the miR-10 family and the TGF-β pathway in GCs. By using bioinformatics approaches, RNA-seq, qPCR, FISH, immunofluorescence, Western blot and luciferase reporter assays, BDNF was identified as a direct target of the miR-10 family in GCs. Additionally, reintroduction of BDNF rescued the effects of miR-10a and miR-10b in GCs. Collectively, miR-10a and miR-10b repressed GC development during folliculogenesis by repressing BDNF and the TGF-β pathway. These effects by the miR-10 family on GCs are conserved among different species.
- Subjects :
- Animals
Apoptosis drug effects
Brain-Derived Neurotrophic Factor metabolism
Cell Line
Cell Proliferation drug effects
Cell Proliferation genetics
Female
Gene Expression Regulation drug effects
Granulosa Cells drug effects
Hormones pharmacology
Humans
Intercellular Signaling Peptides and Proteins pharmacology
Mice
MicroRNAs genetics
Rats
Species Specificity
Transcriptome genetics
Apoptosis genetics
Conserved Sequence
Granulosa Cells cytology
Granulosa Cells metabolism
MicroRNAs metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 7
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 28112253
- Full Text :
- https://doi.org/10.1038/srep41304