title: MiRNA-20 and mirna-106a regulate spermatogonial stem cell renewal at the post-transcriptional level via targeting STAT3 and Ccnd1.
abstract: Studies on spermatogonial stem cells (SSCs) are of unusual significance because they are the unique stem cells that transmit genetic information to subsequent generations and they can acquire pluripotency to become embryonic stem-like cells that have therapeutic applications in human diseases. MicroRNAs (miRNAs) have recently emerged as critical endogenous regulators in mammalian cells. However, the function and mechanisms of individual miRNAs in regulating SSC fate remain unknown. Here, we report for the first time that miRNA-20 and miRNA-106a are preferentially expressed in mouse SSCs. Functional assays in vitro and in vivo using miRNA mimics and inhibitors reveal that miRNA-20 and miRNA-106a are essential for renewal of SSCs. We further demonstrate that these two miRNAs promote renewal at the post-transcriptional level via targeting STAT3 and Ccnd1 and that knockdown of STAT3, Fos, and Ccnd1 results in renewal of SSCs. This study thus provides novel insights into molecular mechanisms regulating renewal and differentiation of SSCs and may have important implications for regulating male reproduction.
authors.affiliation: Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, USA; Clinical Stem Cell Research Center, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Zuping
authors.initials: Z
authors.lastname: He
authors.forename: Jiji
authors.initials: J
authors.lastname: Jiang
authors.forename: Maria
authors.initials: M
authors.lastname: Kokkinaki
authors.forename: Lin
authors.initials: L
authors.lastname: Tang
authors.forename: Wenxian
authors.initials: W
authors.lastname: Zeng
authors.forename: Ian
authors.initials: I
authors.lastname: Gallicano
authors.forename: Ina
authors.initials: I
authors.lastname: Dobrinski
authors.forename: Martin
authors.initials: M
authors.lastname: Dym
mesh_terms: D053687:Adult Stem Cells / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D049109:Cell Proliferation; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000502:physiology*; D005810:Multigene Family; D010641:Phenotype; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D034622:RNA Interference; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D013091:Spermatogenesis / Q000235:genetics; D013737:Testis / Q000166:cytology
chemical_list: C530105:Ccnd1 protein, mouse; D051741:Kruppel-Like Transcription Factors; D035683:MicroRNAs; C543896:Mirn106 microRNA, mouse; C532375:Mirn20 microRNA, mouse; D018809:Proliferating Cell Nuclear Antigen; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C513267:Zbtb16 protein, mouse; D019938:Cyclin D1
keywords: Ccnd1; STAT3; Self-renewal; Spermatogonial stem cells; miRNA-106a; miRNA-20