Macrophage migration inhibitory factor promotes Warburg effect via activation of the NF‑κB/HIF‑1α pathway in lung cancer

  • Authors:
    • Jun Li
    • Junhua Zhang
    • Fengjiao Xie
    • Jiangzhou Peng
    • Xu Wu
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  • Published online on: November 22, 2017     https://doi.org/10.3892/ijmm.2017.3277
  • Pages: 1062-1068
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Abstract

Macrophage migration inhibitory factor (MIF) is upregulated in various solid tumors, a process that is associated with tumor progression and metastasis. The present study aimed to investigate the role and the underlying mechanism of MIF in human lung cancer. Human lung cancer H358, H460, H524, H1650, H838, H1975 and A549 cell lines were used to examine the expression of MIF by real time‑quantitative polymerase chain reaction and western blotting. The lentivirus was used to overexpress MIF and the expression of MIF and hypoxia‑inducible factor 1‑α (HIF‑1α) were knocked down by shRNA or siRNA. The proliferation of cell lines was detected by MTT assay. Glucose uptake, adenosine 5'‑triphosphate (ATP) production, the glycolytic rate and lactate production were used to examine the Warburg effect in cells. BAY 11‑7082 (BAY) was used to inhibit the nuclear translocation of nuclear factor‑κB (NF‑κB), which was detected using immunofluorescence. It was revealed that overexpression of MIF promoted cell proliferation and the Warburg effect in lung cancer, whereas knockdown of MIF inhibited cell proliferation and the Warburg effect. Mechanistically, MIF promoted the Warburg effect by upregulating HIF‑1α. Knockdown of HIF‑1α largely abolished the promotional effect of MIF on the Warburg effect. Additionally, the results in the current study provided evidence that MIF regulates HIF‑1α through NF‑κB. In conclusion, the findings of the present study demonstrated that MIF is a key component in lung cancer progression through promoting the Warburg effect, and that the novel MIF/NF‑κB/HIF‑1α axis may prove to be useful for the development of new strategies for treating patients with lung cancer.
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February-2018
Volume 41 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Li J, Zhang J, Xie F, Peng J and Wu X: Macrophage migration inhibitory factor promotes Warburg effect via activation of the NF‑κB/HIF‑1α pathway in lung cancer. Int J Mol Med 41: 1062-1068, 2018
APA
Li, J., Zhang, J., Xie, F., Peng, J., & Wu, X. (2018). Macrophage migration inhibitory factor promotes Warburg effect via activation of the NF‑κB/HIF‑1α pathway in lung cancer. International Journal of Molecular Medicine, 41, 1062-1068. https://doi.org/10.3892/ijmm.2017.3277
MLA
Li, J., Zhang, J., Xie, F., Peng, J., Wu, X."Macrophage migration inhibitory factor promotes Warburg effect via activation of the NF‑κB/HIF‑1α pathway in lung cancer". International Journal of Molecular Medicine 41.2 (2018): 1062-1068.
Chicago
Li, J., Zhang, J., Xie, F., Peng, J., Wu, X."Macrophage migration inhibitory factor promotes Warburg effect via activation of the NF‑κB/HIF‑1α pathway in lung cancer". International Journal of Molecular Medicine 41, no. 2 (2018): 1062-1068. https://doi.org/10.3892/ijmm.2017.3277