MicroRNA-27 promotes the differentiation of odontoblastic cell by targeting APC and activating Wnt/β-catenin signaling
MicroRNA-27 promotes the differentiation of odontoblastic cell by targeting APC and activating Wnt/β-catenin signaling
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DOI：
10.1016/j.gene.2014.01.045
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发表时间：
2014-04-01
期刊：
影响因子：
3.5
通讯作者：
Kim, Do Kyung
中科院分区：
文献类型：
--
作者：
Park, Min-Gyeong;Kim, Jae-Sung;Kim, Do Kyung
microRNAs（miRNAs）通过抑制mRNA翻译或诱导其降解在调节细胞分化中起重要作用。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的表达在MDPC-23成牙本质细胞分化过程中显著增加。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，而没有细胞增殖。此外，我们的靶基因预测结果显示，与Wnt/beta-catenin信号通路相关的腺瘤性结肠息肉病（APC）mRNA在其3' UTR处具有miR-27结合位点，并被miR-27抑制。随后，miR-27下调的APC通过β-catenin在细胞核中的积累触发Wnt/β-catenin信号转导的激活。我们的数据表明，miR-27通过靶向APC和激活Wnt/β-catenin信号通路促进MDPC-23成牙本质细胞分化。因此，miR-27可能被认为是一个重要的候选人作为成牙本质细胞分化的分子靶点，用于开发基于miRNA的治疗药物在牙科医学。(C)2014爱思唯尔有限公司版权所有。
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/beta-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/beta-catenin signaling through accumulation of beta-catenin in the nucleus. Our data suggest that miR-27 promotes MDPC-23 odontoblastic cell differentiation by targeting APC and activating Wnt/beta-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. (C) 2014 Elsevier B.V. All rights reserved.