title: Targeted Disruption of miR-17-92 Impairs Mouse Spermatogenesis by Activating mTOR Signaling Pathway.
abstract: The miR-17-92 cluster and its 6 different mature microRNAs, including miR-17, miR-18a, miR-19a, miR-20a, miR-19b-1, and miR-92a, play important roles in embryo development, immune system, kidney and heart development, adipose differentiation, aging, and tumorigenicity. Currently, increasing evidence indicates that some members of miR-17-92 cluster may be critical players in spermatogenesis, including miR-17, miR-18a, and miR-20a. However, the roles and underlying mechanisms of miR-17-92 in spermatogenesis remain largely unknown. Our results showed that the targeted disruption of miR-17-92 in the testes of adult mice resulted in severe testicular atrophy, empty seminiferous tubules, and depressed sperm production. This phenotype is partly because of the reduced number of spermatogonia and spermatogonial stem cells, and the significantly increased germ cell apoptosis in the testes of miR-17-92-deficient mice. In addition, overactivation of the mammalian target of rapamycin signaling pathway and upregulation of the pro-apoptotic protein Bim, Stat3, c-Kit, and Socs3 were also observed in miR-17-92-deficient mouse testes, which might be, at least partially if not all, responsible for the aforementioned phenotypic changes in mutant testes. Taken together, these findings suggest that miR-17-92 is essential for normal spermatogenesis in mice.
authors.affiliation: From the Cancer Research Institute, Southern Medical University (RX, XL, HS, FW, WH, TL, XL, YQ, HW, LC, SY, JY, KY, DX, JJ); Institute of Comparative Medicine and Laboratory Animal Center, Southern Medical University (RX, DX); Zhongshan School of Medicine, Sun Yat-sen University (YS); Department of Endocrinology, The Second Affiliated Hospital, Guangzhou Medical University (TD); Department of General Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou (KX); Department of Chemoradiotherapy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou (RX); Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University (KX); Department of Oncology, Nanfang Hospital, Southern Medical University (XR); and Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China (FW).
authors.forename: Raoying
authors.initials: R
authors.lastname: Xie
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Lin
authors.forename: Tao
authors.initials: T
authors.lastname: Du
authors.forename: Kang
authors.initials: K
authors.lastname: Xu
authors.forename: Hongfen
authors.initials: H
authors.lastname: Shen
authors.forename: Fang
authors.initials: F
authors.lastname: Wei
authors.forename: Weichao
authors.initials: W
authors.lastname: Hao
authors.forename: Taoyan
authors.initials: T
authors.lastname: Lin
authors.forename: Xia
authors.initials: X
authors.lastname: Lin
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Qin
authors.forename: Huiyan
authors.initials: H
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Sheng
authors.initials: S
authors.lastname: Yang
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.forename: Xiaoxiang
authors.initials: X
authors.lastname: Rong
authors.forename: Kaitai
authors.initials: K
authors.lastname: Yao
authors.forename: Dong
authors.initials: D
authors.lastname: Xiao
authors.forename: Junshuang
authors.initials: J
authors.lastname: Jia
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D002460:Cell Line; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013091:Spermatogenesis / Q000502:physiology*; D013093:Spermatogonia / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000096:biosynthesis*; D013737:Testis / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; C575895:MIRN17-92 microRNA, mouse; D008565:Membrane Proteins; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D058570:TOR Serine-Threonine Kinases