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

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-alpha (HIF-1 alpha) 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-B (NF-kappa B), 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-1 alpha. Knockdown of HIF-1 largely abolished the promotional effect of MIF on the Warburg effect. Additionally, the results in the current study provided evidence that MIF regulates HIF-1 alpha through NF-kappa B. 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-kappa B/HIF-1 alpha axis may prove to be useful for the development of new strategies for treating patients with lung cancer.