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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.
AuthorsJae-Sung Kim, Min-Gyeong Park, Seul Ah Lee, Sun-Young Park, Heung-Joong Kim, Sun-Kyoung Yu, Chun Sung Kim, Su-Gwan Kim, Ji-Su Oh, Jae-Seek You, Jin-Soo Kim, Yo-Seob Seo, Hong Sung Chun, Joo-Cheol Park, Do Kyung Kim
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 446 Issue 4 Pg. 894-900 (Apr 18 2014) ISSN: 1090-2104 [Electronic] United States
PMID24642258 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier Inc. All rights reserved.
Chemical References
  • Adenomatous Polyposis Coli Protein
  • MIRN663 microRNA, mouse
  • MicroRNAs
  • Wnt Proteins
  • beta Catenin
Topics
  • Adenomatous Polyposis Coli Protein (genetics)
  • Animals
  • Cell Differentiation
  • Cell Line
  • Down-Regulation
  • Genes, APC
  • Mice
  • MicroRNAs (metabolism)
  • Odontogenesis
  • Wnt Proteins (metabolism)
  • Wnt Signaling Pathway
  • beta Catenin (metabolism)

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