title: MiR-153 Regulates Amelogenesis by Targeting Endocytotic and Endosomal/lysosomal Pathways-Novel Insight into the Origins of Enamel Pathologies.
abstract: Amelogenesis imperfecta (AI) is group of inherited disorders resulting in enamel pathologies. The involvement of epigenetic regulation in the pathogenesis of AI is yet to be clarified due to a lack of knowledge about amelogenesis. Our previous genome-wide microRNA and mRNA transcriptome analyses suggest a key role for miR-153 in endosome/lysosome-related pathways during amelogenesis. Here we show that miR-153 is significantly downregulated in maturation ameloblasts compared with secretory ameloblasts. Within ameloblast-like cells, upregulation of miR-153 results in the downregulation of its predicted targets including Cltc, Lamp1, Clcn4 and Slc4a4, and a number of miRNAs implicated in endocytotic pathways. Luciferase reporter assays confirmed the predicted interactions between miR-153 and the 3'-UTRs of Cltc, Lamp1 (in a prior study), Clcn4 and Slc4a4. In an enamel protein intake assay, enamel cells transfected with miR-153 show a decreased ability to endocytose enamel proteins. Finally, microinjection of miR-153 in the region of mouse first mandibular molar at postnatal day 8 (PN8) induced AI-like pathologies when the enamel development reached maturity (PN12). In conclusion, miR-153 regulates maturation-stage amelogenesis by targeting key genes involved in the endocytotic and endosomal/lysosomal pathways, and disruption of miR-153 expression is a potential candidate etiologic factor contributing to the occurrence of AI.
authors.affiliation: Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA.|Department of Orthodontics, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA.
authors.forename: Kaifeng
authors.initials: K
authors.lastname: Yin
authors.affiliation: Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA.
authors.forename: Wenting
authors.initials: W
authors.lastname: Lin
authors.affiliation: Department of Endodontics, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Biochemistry, Akita University of Graduate School of Medicine, Hondo, Akita, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Sugiyama
authors.affiliation: Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA.
authors.forename: Malcolm L
authors.initials: ML
authors.lastname: Snead
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Hacia
authors.affiliation: Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Paine
mesh_terms: D000565:Ameloblasts / Q000378:metabolism; D000566:Amelogenesis; D000567:Amelogenesis Imperfecta / Q000209:etiology / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D003743:Dental Enamel / Q000254:growth & development* / Q000378:metabolism* / Q000473:pathology; D003746:Dental Enamel Proteins / Q000378:metabolism; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000378:metabolism*
chemical_list: D003746:Dental Enamel Proteins; C577878:MIRN153 microRNA, mouse; D035683:MicroRNAs