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http://dx.doi.org/10.7314/APJCP.2014.15.10.4245

miR-186 Regulates Glycolysis through Glut1 During the Formation of Cancer-associated Fibroblasts  

Sun, Pan (Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine)
Hu, Jun-Wei (Shanghai East Hospital Affiliated to Tongji University)
Xiong, Wu-Jun (Shanghai East Hospital Affiliated to Tongji University)
Mi, Jun (Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.15, no.10, 2014 , pp. 4245-4250 More about this Journal
Abstract
Emerging evidence has suggested that glycolysis is enhanced in cancer-associated fibroblasts (CAF), and miR-186 is downregulated during the CAF formation. However, it is not clear whether miR-186 is involved in the regulation of glycolysis and what the role of miR-186 plays during the CAF formation. In this study, quantitative PCR analysises show miR-186 is downregulated during the CAF formation. Moreover, miR-186 targets the 3' UTR of Glut1, and its overexpression results in the degradation of Glut1 mRNA, which eventually reduces the level of Glut1 protein. On the other hand, knockdown of miR-186 increased the expression of Glut1. Both time course and dose response experiments also demonstrated that the protein and mRNA levels of Glut1 increase during CAF formation, according to Western blot and quantitative PCR analyses, respectively. Most importantly, besides the regulation on cell cycle progression, miR-186 regulates glucose uptake and lactate production which is mediated by Glut1. These observations suggest that miR-186 plays important roles in glycolysis regulation as well as cell cycle checkpoint activation.
Keywords
miR-186; Glut1; cancer-associated fibroblast; CDK2;
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