Purpose: Our previous study demonstrated that SIRT6 is upregulated in papillary thyroid cancer (PTC) and enhances tumor aggressiveness. In this study, we further researched its influence in the Warburg effect.
Methods: SIRT6-upregulated and downregulated BCPAP cells and negative control BCPAP-NC groups were generated with lentiviral vectors. In these two cell lines, reactive oxygen species (ROS) were detected by dichlorodihydrofluorescein diacetate. Expression of the key Warburg effect genes including GLUT1, HK2, GAPDH, PGK1, ENO1, PKM2 and LDHA was measured by quantitative real-time PCR and western blotting. Glucose uptake, lactate production and the ATP content of cells were detected with assay kits. The ROS scavenger N -acetylcysteine was used for treatment of BCPAP-SIRT6, and the same measurements as described above were detected again.
Results: Compared with the BCPAP-NC group, expression of the key Warburg effect genes including Glut1, HK2 and GAPDH and their protein products was upregulated in the BCPAP-SIRT6 group, whereas BCPAP-shSIRT6 showed significant downregulation. Meanwhile, ROS, glucose uptake, lactate production and ATP content of the BCPAP-SIRT6 group were also significantly increased, and BCPAP-shSIRT6 showed significant downregulation. Furthermore, upregulation of key Warburg effect genes and glucose uptake, lactate production and ATP content were all rescued after treatment with ROS scavenger.
Conclusion: SIRT6 promoted the Warburg effect of PTC cells via upregulation of ROS. Inhibition of ROS in SIRT6-upregulated cells could rescue activation of the Warburg effect.
Keywords: sirtuin 6, Warburg effect, reactive oxygen species, papillary thyroid cancer