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NAMPT promotes hepatitis B virus replication and liver cancer cell proliferation through the regulation of aerobic glycolysis

  • Authors:
    • Hui‑Jie Guo
    • Hong‑Yu Li
    • Zi‑Hao Chen
    • Wen‑Jing Zhou
    • Jia‑Jie Li
    • Jia‑Yi  Zhang
    • Jing Wang
    • Xing‑Yan Luo
    • Ting Zeng
    • Zhao Shi
    • Chun‑Fen Mo
  • View Affiliations / Copyright

    Affiliations: Department of Immunology, School of Basic Medical Sciences, Chengdu Medical College, Chengdu, Sichuan 610500, P.R. China, Department of Anatomy, Histology and Embryology, Development and Regeneration Key Laboratory of Sichuan Province, Chengdu Medical College, Chengdu, Sichuan 610500, P.R. China
    Copyright: © Guo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 390
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    Published online on: March 18, 2021
       https://doi.org/10.3892/ol.2021.12651
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Abstract

Nicotinamide phosphoribosyltransferase (NAMPT) is a critical rate‑limiting enzyme involved in NAD synthesis that has been shown to contribute to the progression of liver cancer. However, the potential role and mechanism of NAMPT in hepatitis B virus (HBV)‑associated liver cancer remain unclear. The present study assessed the expression of NAMPT in HBV‑positive and ‑negative liver cancer cells, and investigated whether HBV‑induced NAMPT expression is dependent on HBV X protein (HBx). In addition, the role of NAMPT in HBV replication and transcription, and in HBV‑mediated liver cancer cell growth was explored. The effects of NAMPT on the glycolytic pathway were also evaluated. Reverse transcription‑quantitative PCR and western blotting results revealed that NAMPT expression levels were significantly higher in HBV‑positive liver cancer cells than in HBV‑negative liver cancer cells, and this effect was HBx‑dependent. Moreover, the activation of NAMPT was demonstrated to be required for HBV replication and transcription. The NAMPT inhibitor FK866 repressed cell survival and promoted cell death in HBV‑expressing liver cancer cells, and these effects were attenuated by nicotinamide mononucleotide. Furthermore, the inhibition of NAMPT was associated with decreased glucose uptake, decreased lactate production and decreased ATP levels in HBV‑expressing liver cancer cells, indicating that NAMPT may promote the aerobic glycolysis. Collectively, these findings reveal a positive feedback loop in which HBV enhances NAMPT expression and the activation of NAMPT promotes HBV replication and HBV‑mediated malignant cell growth in liver cancer. The present study highlights the important role of NAMPT in the regulation of aerobic glycolysis in HBV‑mediated liver cancer, and suggests that NAMPT may be a promising treatment target for patients with HBV‑associated liver cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Guo HJ, Li HY, Chen ZH, Zhou WJ, Li JJ, Zhang JY, Wang J, Luo XY, Zeng T, Shi Z, Shi Z, et al: NAMPT promotes hepatitis B virus replication and liver cancer cell proliferation through the regulation of aerobic glycolysis. Oncol Lett 21: 390, 2021.
APA
Guo, H., Li, H., Chen, Z., Zhou, W., Li, J., Zhang, J. ... Mo, C. (2021). NAMPT promotes hepatitis B virus replication and liver cancer cell proliferation through the regulation of aerobic glycolysis. Oncology Letters, 21, 390. https://doi.org/10.3892/ol.2021.12651
MLA
Guo, H., Li, H., Chen, Z., Zhou, W., Li, J., Zhang, J., Wang, J., Luo, X., Zeng, T., Shi, Z., Mo, C."NAMPT promotes hepatitis B virus replication and liver cancer cell proliferation through the regulation of aerobic glycolysis". Oncology Letters 21.5 (2021): 390.
Chicago
Guo, H., Li, H., Chen, Z., Zhou, W., Li, J., Zhang, J., Wang, J., Luo, X., Zeng, T., Shi, Z., Mo, C."NAMPT promotes hepatitis B virus replication and liver cancer cell proliferation through the regulation of aerobic glycolysis". Oncology Letters 21, no. 5 (2021): 390. https://doi.org/10.3892/ol.2021.12651
Copy and paste a formatted citation
x
Spandidos Publications style
Guo HJ, Li HY, Chen ZH, Zhou WJ, Li JJ, Zhang JY, Wang J, Luo XY, Zeng T, Shi Z, Shi Z, et al: NAMPT promotes hepatitis B virus replication and liver cancer cell proliferation through the regulation of aerobic glycolysis. Oncol Lett 21: 390, 2021.
APA
Guo, H., Li, H., Chen, Z., Zhou, W., Li, J., Zhang, J. ... Mo, C. (2021). NAMPT promotes hepatitis B virus replication and liver cancer cell proliferation through the regulation of aerobic glycolysis. Oncology Letters, 21, 390. https://doi.org/10.3892/ol.2021.12651
MLA
Guo, H., Li, H., Chen, Z., Zhou, W., Li, J., Zhang, J., Wang, J., Luo, X., Zeng, T., Shi, Z., Mo, C."NAMPT promotes hepatitis B virus replication and liver cancer cell proliferation through the regulation of aerobic glycolysis". Oncology Letters 21.5 (2021): 390.
Chicago
Guo, H., Li, H., Chen, Z., Zhou, W., Li, J., Zhang, J., Wang, J., Luo, X., Zeng, T., Shi, Z., Mo, C."NAMPT promotes hepatitis B virus replication and liver cancer cell proliferation through the regulation of aerobic glycolysis". Oncology Letters 21, no. 5 (2021): 390. https://doi.org/10.3892/ol.2021.12651
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