title: MiR-140 is co-expressed with Wwp2-C transcript and activated by Sox9 to target Sp1 in maintaining the chondrocyte proliferation.
abstract: MiR-140 is a microRNA specially involved in chondrogenesis and osteoarthritis pathogenesis. However, its transcriptional regulation and target genes in cartilage development are not fully understood. Here we detected that miR-140 was uniquely expressed in chondrocyte and suppressed by Wnt/β-catenin signalling. The miR-140 primary transcript was an intron-retained RNA co-expressed with Wwp2-C isoform, which was directly induced by Sox9 through binding to the intron 10 of Wwp2 gene. Knockdown of miR-140 in limb bud micromass cultures resulted in arrest of chondrogenic proliferation. Sp1, the activator of the cell cycle regulator p15(INK4b), was identified as a target of miR-140 in maintaining the chondrocyte proliferation. Collectively, our findings expand our understanding of the transcriptional regulation and the chondrogenic role of miR-140 in chondrogenesis.
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Shengying
authors.initials: S
authors.lastname: Qin
authors.forename: Chengqing
authors.initials: C
authors.lastname: Yi
authors.forename: Gang
authors.initials: G
authors.lastname: Ma
authors.forename: Huang
authors.initials: H
authors.lastname: Zhu
authors.forename: Wenrong
authors.initials: W
authors.lastname: Zhou
authors.forename: Yuyu
authors.initials: Y
authors.lastname: Xiong
authors.forename: Xuming
authors.initials: X
authors.lastname: Zhu
authors.forename: Yujiong
authors.initials: Y
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: He
authors.forename: Xizhi
authors.initials: X
authors.lastname: Guo
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D019902:Chondrocytes / Q000166:cytology / Q000502:physiology*; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D018878:Limb Buds / Q000033:anatomy & histology / Q000196:embryology; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: C547828:MIRN140 microRNA, mouse; D035683:MicroRNAs; D055758:SOX9 Transcription Factor; D016329:Sp1 Transcription Factor; C487995:Wwp2 protein, mouse; D044767:Ubiquitin-Protein Ligases