期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 19, 期 3, 页码 -出版社
MDPI
DOI: 10.3390/ijms19030773
关键词
mouse; miR-25-3p; Akt1; AP-2 alpha; promoter; cell metabolism
资金
- China Postdoctoral Science Foundation [2017M610465]
- Open Project of Key Laboratory of Animal Embryo Engineering and Molecular Breeding of Hubei Province [KLAEMB201602]
- Postdoctoral Innovation Post of Hubei Province
- National Natural Science Foundation of China [31472075, 31402051, 31501932]
- Natural Science Foundation of Hubei Province key projects of technical innovation [2016ABA117]
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据