title: MicroRNA-16 Modulates Melatonin-Induced Cell Growth in the Mouse-Derived Spermatogonia Cell Line GC-1 spg Cells by Targeting Ccnd1.
abstract: Melatonin exerts a range of physiological effects. However, the functional significance of melatonin in spermatogenesis and the underlying mechanisms remain unclear. MicroRNAs (miRNAs) are essential in the initiation and progression of testicular development, including spermatogenesis. Thus far, limited information is known about the role of miRNAs in melatonin-mediated spermatogenesis. In this study, the expression levels of testicular miRNA machinery genes, namely, Dgcr8 and Xpo5, were significantly increased by melatonin. The miRNA expression profile was identified in the testes of melatonin-treated mice. Ten miRNAs were significantly up-regulated, and 15 miRNAs were down-regulated. Melatonin (25 μM) enhanced cell growth and reduced apoptosis in GC-1 spg cells. Among the down-regulated miRNAs, miR-16 expression was influenced by melatonin in GC-1 spg cells. The miR-16 mimics in GC-1 spg cells significantly suppressed cell growth and promoted cell apoptosis. Conversely, transfection of the miR-16 inhibitor significantly increased cell growth and decreased cell apoptosis. The protein expression level of CCND1 (Cyclin D1) in GC-1 spg cells was decreased by the miR-16 mimics and increased by knockdown of miR-16. Moreover, bioinformatics and reporter activity analyses showed that Ccnd1 was a potential target of miR-16. These results suggested that miR-16 may function as a novel regulator of testicular functions during melatonin stimulation by targeting Ccnd1.
authors.affiliation: College of Animal Sciences, Jilin Provincial Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun, Jilin, P.R. of China.
authors.forename: Chunjin
authors.initials: C
authors.lastname: Li
authors.affiliation: College of Animal Sciences, Jilin Provincial Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun, Jilin, P.R. of China.
authors.forename: Shuxiong
authors.initials: S
authors.lastname: Chen
authors.affiliation: College of Animal Sciences, Jilin Provincial Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun, Jilin, P.R. of China.
authors.forename: Hongjiao
authors.initials: H
authors.lastname: Li
authors.affiliation: College of Animal Sciences, Jilin Provincial Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun, Jilin, P.R. of China.
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.affiliation: College of Animal Sciences, Jilin Provincial Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun, Jilin, P.R. of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: College of Animal Sciences, Jilin Provincial Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun, Jilin, P.R. of China.
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: College of Animal Sciences, Jilin Provincial Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun, Jilin, P.R. of China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Liu
authors.affiliation: College of Animal Sciences, Jilin Provincial Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun, Jilin, P.R. of China.
authors.forename: Yating
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Animal Sciences, Jilin Provincial Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun, Jilin, P.R. of China.
authors.forename: Shan
authors.initials: S
authors.lastname: Gao
authors.affiliation: College of Animal Sciences, Jilin Provincial Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun, Jilin, P.R. of China.
authors.forename: Fengge
authors.initials: F
authors.lastname: Wang
authors.affiliation: College of Animal Sciences, Jilin Provincial Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun, Jilin, P.R. of China.
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Yu
authors.affiliation: College of Animal Sciences, Jilin Provincial Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun, Jilin, P.R. of China.
authors.forename: Haotian
authors.initials: H
authors.lastname: Wang
authors.affiliation: College of Animal Sciences, Jilin Provincial Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun, Jilin, P.R. of China.
authors.forename: Jiahui
authors.initials: J
authors.lastname: Rao
authors.affiliation: College of Animal Sciences, Jilin Provincial Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun, Jilin, P.R. of China xzhou65@vip.sina.com.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects* / Q000502:physiology; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D013093:Spermatogonia / Q000187:drug effects / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; C522604:Mirn16 microRNA, mouse; D019938:Cyclin D1; D008550:Melatonin
keywords: Ccnd1; GC-1 spg cell growth; melatonin; miR-16; mice