title: A novel negative regulator of adipogenesis: microRNA-363.
abstract: The differentiation of adipose tissue-derived stromal cells (ADSCs) into adipocytes involves a highly orchestrated series of events that includes cell lineage commitment, mitotic clonal expansion, growth arrest, and terminal differentiation. However, the molecular mechanisms controlling adipogenesis are not yet completely understood. In this study, we investigated whether microRNAs (miRNAs) play a role in adipocyte differentiation. Microarray analysis was performed to determine the miRNA expression profile during ADSC differentiation, and miR-363 was found to be one of the most significantly downregulated miRNAs. We show that the overexpression of miR-363 in ADSCs inhibited mitotic clonal expansion and terminal differentiation. Furthermore, ectopic introduction of miR-363 into ADSCs markedly reduced the levels of E2F3, a key transcription factor that regulates growth and proliferation during mitotic clonal expansion. Finally, using an EGFP/RFP reporter assay, we demonstrate that miR-363 can directly target the 3'UTR of E2F3. Taken together, these results suggest that miR-363 regulates the transition from mitotic clonal expansion to terminal differentiation during adipogenesis in ADSCs, at least in part, by targeting E2F3.
authors.affiliation: State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, People's Republic of China; Department of Oral & Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Junhui
authors.initials: J
authors.lastname: Cui
authors.forename: Jia
authors.initials: J
authors.lastname: Hou
authors.forename: Jie
authors.initials: J
authors.lastname: Long
authors.forename: Cai
authors.initials: C
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
mesh_terms: D020413:3' Untranslated Regions; D017667:Adipocytes / Q000166:cytology; D050156:Adipogenesis / Q000235:genetics*; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage; D050699:E2F3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D050699:E2F3 Transcription Factor; C098319:E2F3 protein, human; C574861:MIRN363 microRNA, human; D035683:MicroRNAs
keywords: Adipogenesis; Adipose tissue-derived stromal cells; Cell cycle; Clonal expansion; E2F3; MicroRNA-363