title: Conserved miR-10 family represses proliferation and induces apoptosis in ovarian granulosa cells.
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.
authors.affiliation: Chinese University of Hong Kong - Shandong University Joint Laboratory for Reproductive Genetics, School of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, SAR, Hong Kong.
authors.forename: Tu
authors.initials: T
authors.lastname: Jiajie
authors.affiliation: Chinese University of Hong Kong - Shandong University Joint Laboratory for Reproductive Genetics, School of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, SAR, Hong Kong.|Key Laboratory of Fertility Preservation and Maintenance, Ministry of Education, Key Laboratory of Reproduction and Genetics in Ningxia, Department of Histology and Embryology, Ningxia Medical University, Yinchuan, Ningxia, 75004, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yanzhou
authors.affiliation: Chinese University of Hong Kong - Shandong University Joint Laboratory for Reproductive Genetics, School of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, SAR, Hong Kong.
authors.forename: Albert Cheung
authors.initials: AC
authors.lastname: Hoi-Hung
authors.affiliation: Center for Reproductive Medicine; National Research Center for Assisted Reproductive Technology and Reproductive Genetics; The Key Laboratory for Reproductive Endocrinology of Ministry of Education; Shandong Provincial Key Laboratory of Reproductive Medicine, Provincial Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zi-Jiang
authors.affiliation: Chinese University of Hong Kong - Shandong University Joint Laboratory for Reproductive Genetics, School of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, SAR, Hong Kong.
authors.forename: Chan
authors.initials: C
authors.lastname: Wai-Yee
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D017124:Conserved Sequence; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006107:Granulosa Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D013045:Species Specificity; D059467:Transcriptome / Q000235:genetics
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D006728:Hormones; D036341:Intercellular Signaling Peptides and Proteins; D035683:MicroRNAs