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A lentiviral sponge for miRNA-21 diminishes aerobic glycolysis in bladder cancer T24 cells via the PTEN/PI3K/AKT/mTOR axis

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Tumor Biology

Abstract

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-1α)] 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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Acknowledgments

This work was supported by the Program for Development of Innovative Research Team of the First Affiliated Hospital of Nanjing Medical University, the Provincial Initiative Program for Excellency Disciplines of Jiangsu Province, the National Natural Science Foundation of China (grant Nos. 81272832 and 81201997), the Natural Science Foundation of Jiangsu Province (grant No. BK2011848), the Six Major Talent Peak Project of Jiangsu Province (grant No. 2011-WS-121), the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) and Jiangsu Provincial Special Program of Medical Science (BL2012027). The funders had no role in study design, data collection and analysis; decision to publish; or preparation of the manuscript.

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Authors and Affiliations

  1. Department of Urology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China

    Xiao Yang, Yidong Cheng, Pengchao Li, Jun Tao, Xiaheng Deng, Xiaolei Zhang, Min Gu, Qiang Lu & Changjun Yin

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  1. Xiao Yang
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  2. Yidong Cheng
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  3. Pengchao Li
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  4. Jun Tao
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  5. Xiaheng Deng
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  6. Xiaolei Zhang
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  7. Min Gu
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  8. Qiang Lu
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  9. Changjun Yin
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Corresponding authors

Correspondence to Min Gu or Qiang Lu.

Additional information

Xiao Yang, Yidong Cheng and Pengchao Li contributed equally to this work.

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Yang, X., Cheng, Y., Li, P. et al. A lentiviral sponge for miRNA-21 diminishes aerobic glycolysis in bladder cancer T24 cells via the PTEN/PI3K/AKT/mTOR axis. Tumor Biol. 36, 383–391 (2015). https://doi.org/10.1007/s13277-014-2617-2

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  • DOI: https://doi.org/10.1007/s13277-014-2617-2

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