title: miR-449a regulates the chondrogenesis of human mesenchymal stem cells through direct targeting of lymphoid enhancer-binding factor-1.
abstract: microRNAs are small molecules, about 17-23 nucleotides in length, that act as translational regulators of their target gene. By binding to a target, microRNAs are known to either inhibit translation or induce degradation of the target. Despite the great interest in microRNAs, however, the exact targets of each individual microRNA in different processes remain largely unknown. In this study, we determined that the lymphoid enhancer-binding factor-1 (LEF-1) was expressed during the chondrogenesis of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) and sought to identify a novel microRNA targeting this gene. Through subsequent studies, we have identified, for the first time, one particular microRNA, miR-449a, that recognizes and regulates the expression of LEF-1 in a dose-dependent and sequence-specific manner. In addition, we observed that the inhibition of LEF-1 via miR-449a led to the subsequent repression of Sox 9, which is a well-established regulator of chondrogenesis. Collectively, this study demonstrated that miR-449a directly targets LEF-1, which in turn affects the expression of Sox 9, ultimately leading to the proper regulation of the differentiation and chondrogenesis of human MSCs (hBM-MSCs).
authors: Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, South Korea.
authors: Seungil
authors: S
authors: Paik
authors: Ho Sun
authors: HS
authors: Jung
authors: Seulgi
authors: S
authors: Lee
authors: Dong Suk
authors: DS
authors: Yoon
authors: Min Sung
authors: MS
authors: Park
authors: Jin Woo
authors: JW
authors: Lee
mesh_terms: D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D020219:Chondrogenesis / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics* / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D055758:SOX9 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: C497573:LEF1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1; C544530:MIRN449 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human