Sun Pan, Hu Jun-Wei, Xiong Wu-Jun, Mi Jun
Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, China E-mail :
Asian Pac J Cancer Prev. 2014;15(10):4245-50. doi: 10.7314/apjcp.2014.15.10.4245.
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.
新出现的证据表明，癌症相关成纤维细胞（CAF）中的糖酵解增强，且在CAF形成过程中miR-186表达下调。然而，尚不清楚miR-186是否参与糖酵解的调控，以及miR-186在CAF形成过程中发挥何种作用。在本研究中，定量PCR分析显示在CAF形成过程中miR-186表达下调。此外，miR-186靶向Glut1的3'UTR，其过表达导致Glut1 mRNA降解，最终降低Glut1蛋白水平。另一方面，敲低miR-186可增加Glut1的表达。时间进程和剂量反应实验也均表明，根据蛋白质印迹和定量PCR分析，在CAF形成过程中Glut1的蛋白质和mRNA水平均升高。最重要的是，除了对细胞周期进程的调控外，miR-186还调控由Glut1介导的葡萄糖摄取和乳酸生成。这些观察结果表明，miR-186在糖酵解调控以及细胞周期检查点激活中发挥重要作用。
