title: miR-186 regulates glycolysis through Glut1 during the formation of cancer-associated fibroblasts.
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.
authors.affiliation: 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 : xiongwujun@126.com, jmei@sjtu.edu.cn.
authors.forename: Pan
authors.initials: P
authors.lastname: Sun
authors.forename: Jun-Wei
authors.initials: JW
authors.lastname: Hu
authors.forename: Wu-Jun
authors.initials: WJ
authors.lastname: Xiong
authors.forename: Jun
authors.initials: J
authors.lastname: Mi
mesh_terms: D001692:Biological Transport / Q000235:genetics; D059447:Cell Cycle Checkpoints / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation; D015536:Down-Regulation; D005347:Fibroblasts; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000235:genetics*; D006019:Glycolysis / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering
chemical_list: D051272:Glucose Transporter Type 1; C533096:MIRN186 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C495677:SLC2A1 protein, human; D005947:Glucose