title: Downregulation of adenomatous polyposis coli by microRNA-663 promotes odontogenic differentiation through activation of Wnt/beta-catenin signaling.
abstract: MicroRNAs (miRNAs) regulate cell differentiation by inhibiting mRNA translation or by inducing its degradation. However, the role of miRNAs in odontogenic differentiation is largely unknown. In this present study, we observed that the expression of miR-663 increased significantly during differentiation of MDPC-23 cells to odontoblasts. Furthermore, up-regulation of miR-663 expression promoted odontogenic differentiation and accelerated mineralization without proliferation in MDPC-23 cells. In addition, target gene prediction for miR-663 revealed that the mRNA of the adenomatous polyposis coli (APC) gene, which is associated with the Wnt/β-catenin signaling pathway, has a miR-663 binding site in its 3'-untranslated region (3'UTR). Furthermore, APC expressional was suppressed significantly by miR-663, and this down-regulation of APC expression triggered activation of Wnt/β-catenin signaling through accumulation of β-catenin in the nucleus. Taken together, these findings suggest that miR-663 promotes differentiation of MDPC-23 cells to odontoblasts by targeting APC-mediated activation of Wnt/β-catenin signaling. Therefore, miR-663 can be considered a critical regulator of odontoblast differentiation and can be utilized for developing miRNA-based therapeutic agents.
authors.affiliation: Oral Biology Research Institute, School of Dentistry, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Jae-Sung
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Oral Biology Research Institute, School of Dentistry, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Min-Gyeong
authors.initials: MG
authors.lastname: Park
authors.affiliation: Oral Biology Research Institute, School of Dentistry, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Seul Ah
authors.initials: SA
authors.lastname: Lee
authors.affiliation: Oral Biology Research Institute, School of Dentistry, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Park
authors.affiliation: Oral Biology Research Institute, School of Dentistry, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Heung-Joong
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Oral Biology Research Institute, School of Dentistry, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Sun-Kyoung
authors.initials: SK
authors.lastname: Yu
authors.affiliation: Oral Biology Research Institute, School of Dentistry, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Chun Sung
authors.initials: CS
authors.lastname: Kim
authors.affiliation: Oral Biology Research Institute, School of Dentistry, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Su-Gwan
authors.initials: SG
authors.lastname: Kim
authors.affiliation: Oral Biology Research Institute, School of Dentistry, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Ji-Su
authors.initials: JS
authors.lastname: Oh
authors.affiliation: Oral Biology Research Institute, School of Dentistry, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Jae-Seek
authors.initials: JS
authors.lastname: You
authors.affiliation: Oral Biology Research Institute, School of Dentistry, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Jin-Soo
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Oral Biology Research Institute, School of Dentistry, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Yo-Seob
authors.initials: YS
authors.lastname: Seo
authors.affiliation: Department of Biomedical Science, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Hong Sung
authors.initials: HS
authors.lastname: Chun
authors.affiliation: Department of Oral Histology-Developmental Biology, School of Dentistry and Dental Research Institute, BK 21, Seoul National University, Seoul 110-749, Republic of Korea.
authors.forename: Joo-Cheol
authors.initials: JC
authors.lastname: Park
authors.affiliation: Oral Biology Research Institute, School of Dentistry, Chosun University, Gwangju 501-759, Republic of Korea. Electronic address: kdk@chosun.ac.kr.
authors.forename: Do Kyung
authors.initials: DK
authors.lastname: Kim
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D015536:Down-Regulation; D017491:Genes, APC; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D009805:Odontogenesis; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: D025601:Adenomatous Polyposis Coli Protein; C000589045:MIRN663 microRNA, mouse; D035683:MicroRNAs; D051153:Wnt Proteins; D051176:beta Catenin
keywords: Adenomatous polyposis coli; Differentiation; Odontoblasts; miR-663; β-Catenin