miR-25-3p, Positively Regulated by Transcription Factor AP-2 alpha, Regulates the Metabolism of C2C12 Cells by Targeting Akt1

文献类型： 外文期刊

第一作者： Zhang, Feng

作者： Zhang, Feng;Tao, Hu;Xiong, Qi;Liu, Yang;Chen, Mingxin;Zhang, Feng;Chen, Kun;Kang, Tingting;Zeng, Qianhui;Jiang, Siwen;Zhang, Feng;Chen, Kun;Kang, Tingting;Zeng, Qianhui;Jiang, Siwen

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关键词： mouse; miR-25-3p; Akt1; AP-2 alpha; promoter; cell metabolism

期刊名称：INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES （ 影响因子：5.923； 五年影响因子：6.132 ）

ISSN： 1422-0067

年卷期： 2018 年 19 卷 3 期

页码：

收录情况： SCI

摘要： miR-25, a member of the miR-106b-25 cluster, has been reported as playing an important role in many biological processes by numerous studies, while the role of miR-25 in metabolism and its transcriptional regulation mechanism remain unclear. In this study, gain-of-function and loss-of-function assays demonstrated that miR-25-3p positively regulated the metabolism of C2C12 cells by attenuating phosphoinositide 3-kinase (PI3K) gene expression and triglyceride (TG) content, and enhancing the content of adenosine triphosphate (ATP) and reactive oxygen species (ROS). Furthermore, the results from bioinformatics analysis, dual luciferase assay, site-directed mutagenesis, qRT-PCR, and Western blotting demonstrated that miR-25-3p directly targeted the AKT serine/threonine kinase 1 (Akt1) 3' untranslated region (3'UTR). The core promoter of miR-25-3p was identified, and the transcription factor activator protein-2 alpha (AP-2 alpha) significantly increased the expression of mature miR-25-3p by binding to its core promoter in vivo, as indicated by the chromatin immunoprecipitation (ChIP) assay, and AP-2 alpha binding also downregulated the expression of Aka. Taken together, our findings suggest that miR-25-3p, positively regulated by the transcription factor AP-2 alpha, enhances C2C12 cell metabolism by targeting the Akt1 gene.

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