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微小 RNA-27 通过靶向 APC 并激活 Wnt/β-连环蛋白信号通路促进成牙本质细胞的分化。

MicroRNA-27 promotes the differentiation of odontoblastic cell by targeting APC and activating Wnt/β-catenin signaling.

机构信息

Oral Biology Research Institute, Chosun University School of Dentistry, Gwangju 501-759, Republic of Korea.

Department of Biotechnology, Chosun University, Gwangju 501-759, Republic of Korea.

出版信息

Gene. 2014 Apr 1;538(2):266-72. doi: 10.1016/j.gene.2014.01.045. Epub 2014 Jan 30.

Abstract

MicroRNAs (miRNAs) play an essential role in regulating cell differentiation either by inhibiting mRNA translation or by inducing its degradation. However, the role of miRNAs in odontoblastic cell differentaion is largely unknown. In the present study, we demonstrate that the expression of miR-27 was significantly increased during MDPC-23 odontoblastic cell differentiation. Furthermore, the up-regulation of miR-27 promotes the differentiation of MDPC-23 odontoblastic cells and accelerates mineralization without cell proliferation. In addition, our results of target gene prediction revealed that the mRNA of adenomatous polyposis coli (APC) associated with Wnt/β-catenin signaling pathway has miR-27 binding site in the its 3' UTR and is suppressed by miR-27. Subsequentially, the down-regulated APC by miR-27 triggered the activation of Wnt/β-catenin signaling through accumulation of β-catenin in the nucleus. Our data suggest that miR-27 promotes MDPC-23 odontoblastic cell differentiation by targeting APC and activating Wnt/β-catenin signaling. Therefore, miR-27 might be considered a critical candidate as an odontoblastic differentiation molecular target for the development of miRNA based therapeutic agents in the dental medicine.

摘要

微小 RNA(miRNAs)通过抑制 mRNA 翻译或诱导其降解,在细胞分化中发挥重要作用。然而,miRNAs 在成牙本质细胞分化中的作用在很大程度上是未知的。在本研究中,我们证明了 miR-27 在 MDPC-23 成牙本质细胞分化过程中的表达显著增加。此外,miR-27 的上调促进了 MDPC-23 成牙本质细胞的分化,并加速了矿化而不促进细胞增殖。此外,我们的靶基因预测结果表明,与 Wnt/β-catenin 信号通路相关的腺瘤性结肠息肉病基因(APC)的 mRNA 在其 3'UTR 中具有 miR-27 结合位点,并被 miR-27 抑制。随后,miR-27 下调 APC 通过β-catenin 在核内积累触发 Wnt/β-catenin 信号的激活。我们的数据表明,miR-27 通过靶向 APC 并激活 Wnt/β-catenin 信号促进 MDPC-23 成牙本质细胞分化。因此,miR-27 可能被认为是一种关键的候选物,作为牙科医学中基于 miRNA 的治疗剂开发的成牙本质细胞分化分子靶点。

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