| 论文题目: | MicroRNA-142-3p Negatively Regulates Canonical Wnt Signaling Pathway |
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| 作者: | Hu Tanyu, Phiwpan Krung, Guo Jitao, Zhang Wei, Guo Jie, Zhang Zhongmei, Zou Mangge, Zhang Xuejie, Zhang Jianhua, and Zhou Xuyu*. |
| 联系作者: | |
| 刊物名称: | PLoS One |
| 期: | |
| 卷: | 11 |
| 页: | e0158432 |
| 年份: | 2016 |
| 影响因子: | 3.535 |
| 论文下载: | 下载地址 |
| 摘要: | Wnt/beta-catenin signaling pathway plays essential roles in mammalian development and tissue homeostasis. MicroRNAs (miRNAs) are a class of regulators involved in modulating this pathway. In this study, we screened miRNAs regulating Wnt/beta-catenin signaling by using a TopFlash based luciferase reporter. Surprisingly, we found that miR-142 inhibited Wnt/beta-catenin signaling, which was inconsistent with a recent study showing that miR-142-3p targeted Adenomatous Polyposis Coli (APC) to upregulate Wnt/beta-catenin signaling. Due to the discordance, we elaborated experiments by using extensive mutagenesis, which demonstrated that the stem-loop structure was important for miR-142 to efficiently suppress Wnt/beta-catenin signaling. Moreover, the inhibitory effect of miR-142 relies on miR-142-3p rather than miR-142-5p. Further, we found that miR-142-3p directly modulated translation of Ctnnb1 mRNA (encoding beta-catenin) through binding to its 3' untranslated region (3' UTR). Finally, miR-142 was able to repress cell cycle progression by inhibiting active Wnt/beta-catenin signaling. Thus, our findings highlight the inhibitory role of miR-142-3p in Wnt/beta-catenin signaling, which help to understand the complex regulation of Wnt/beta-catenin signaling. |
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