期刊
TUMOR BIOLOGY
卷 36, 期 1, 页码 383-391出版社
SPRINGER
DOI: 10.1007/s13277-014-2617-2
关键词
MicroRNA-21; Lentiviral sponge; Bladder cancer; Aerobic glycolysis; Warburg effect
类别
资金
- Program for Development of Innovative Research Team of the First Affiliated Hospital of Nanjing Medical University
- Provincial Initiative Program for Excellency Disciplines of Jiangsu Province
- National Natural Science Foundation of China [81272832, 81201997]
- Natural Science Foundation of Jiangsu Province [BK2011848]
- Six Major Talent Peak Project of Jiangsu Province [2011-WS-121]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- Jiangsu Provincial Special Program of Medical Science [BL2012027]
Cancer cells exhibit the ability to metabolise glucose to lactate even under aerobic conditions for energy. This phenomenon is known as the Warburg effect and can be a potential target to kill cancer cells. Several studies have shown evidence for interplay between microRNAs and key metabolic enzyme effecters, which can facilitate the Warburg effect in cancer cells. In the present study, a microRNA sponge forcibly expressed using a lentiviral vector was utilised to knock down miR-21 expression in vitro. qPCR and Western blot assays were performed to evaluate the expression of a regulatory factor related to aerobic glycolysis and the signalling pathway it regulates. In bladder cancer specimens, expression levels of glycolysis-related genes [glucose transporter (GLUT)1, GLUT3, lactic dehydrogenase (LDH)A, LDHB, hexokinase (HK)1, HK2, pyruvate kinase type M (PKM) and hypoxia-inducible factor 1-alpha (HIF-1 alpha)] were higher in tumour tissues than in adjacent tissues, suggesting the role of glycolysis in bladder cancer. miR-21 inhibition in bladder cancer cell lines resulted in reduction in tumour aerobic glycolysis. Decrease in glucose uptake and lactate production was observed upon expression of the miR-21 sponge, which promoted phosphatase and tensin homologue (PTEN) expression, decreased phosphorylated AKT and deactivated mTOR. Furthermore, messenger RNA (mRNA) and protein expression levels of glycolysis-related genes were also lower in miR-21 sponge cells compared to miR-21 control cells. Our findings suggest that miR-21 acts as a molecular switch to regulate aerobic glycolysis in bladder cancer cells via the PTEN/phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway. Blocking miR-21 function can be an effective diagnostic and therapeutic approach either by itself or in combination with existing methods to treat bladder cancer.
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