期刊
ONCOTARGET
卷 6, 期 15, 页码 13006-13018出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.3514
关键词
let-7a microRNA; c-Myc; hnRNPA1; PKM2; glucose metabolism; aerobic glycolysis; glioma
资金
- National High Technology Research and Development Program of China [2012AA02A508]
- International Cooperation Program [2012DFA30470]
- National Natural Science Foundation of China (National Natural Science Foundation of China) [91229121, 81272792, 81472362, 81372709, 81302185]
- Jiangsu Province's Natural Science Foundation [20131019]
- Jiangsu Province's Key Provincial Talents Program [RC2011051]
- Jiangsu Province's Key Discipline of Medicine [XK201117]
- Jiangsu Provincial Special Program of Medical Science [BL2012028]
- Program for Development of Innovative Research Team in the First Affiliated Hospital of NJMU
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
Tumor cells metabolize more glucose to lactate in aerobic or hypoxic conditions than non-tumor cells. Pyruvate kinase isoenzyme type M2 (PKM2) is crucial for tumor cell aerobic glycolysis. We established a role for let-7a/c-Myc/hnRNPA1/PKM2 signaling in glioma cell glucose metabolism. PKM2 depletion via siRNA inhibits cell proliferation and aerobic glycolysis in glioma cells. C-Myc promotes up-regulation of hnRNPA1 expression, hnRNPA1 binding to PKM pre-mRNA, and the subsequent formation of PKM2. This pathway is downregulated by the microRNA let-7a, which functionally targets c-Myc, whereas hnRNPA1 blocks the biogenesis of let-7a to counteract its ability to downregulate the c-Myc/hnRNPA1/PKM2 signaling pathway. The down-regulation of c-Myc/hnRNPA1/PKM2 by let-7a is verified using a glioma xenograft model. These results suggest that let-7a, c-Myc and hnRNPA1 from a feedback loop, thereby regulating PKM2 expression to modulate glucose metabolism of glioma cells. These findings elucidate a new pathway mediating aerobic glycolysis in gliomas and provide an attractive potential target for therapeutic intervention.
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