A novel mechanism of Sarcoma tyrosine kinase-mediated Glucose-6-phosphatedehydrogenase nuclear localization targeting and regulating N-Myc downstream regulated gene 1 to promote the growth and metastasis of bladder cancer cells
Objective To explore the function and mechanism of Glucose-6-phosphate dehydrogen-ase(G6PD)and Sarcoma tyrosine kinase(Src)in the development of bladder cancer.Methods Collect cancer tissues and adjacent tissues from 30 bladder cancer patients who underwent bladder tumor resection at the Second Affiliated Hospital of Wenzhou Medical University from December 2012 to December 2018.We detected the expression of G6PD and SRC in cancer tissues and paracancerous tissues of bladder cancer patients.Meanwhile,we detected the cell proliferation,apoptosis and migration abilities in T24 and J82 cells through interfering the expression levels of G6PD and SRC,respectively.Finally,the function of pro-moting bladder cancer progression was confirmed by interfering with SRC combined with G6PD overexpres-sion.Results The expression levels of G6PD in tumor group were higher than those in control group(1.07 vs.0.58,t=2.80,P＜0.05).The expression levels of SRC in tumor group were higher than those in control group(0.96 vs.0.54,t=3.25,P＜0.01).After interfering with SRC and G6PD,the proportion of cells in the S phase was higher in the SRC interference group compared to the control group(26.47 vs.32.75,t=2.87,P＜0.05),and also higher in the G6PD interference group compared to the control group(26.47 vs.32.26,t=2.85,P＜0.05).The apoptosis rate of cells was higher in both the SRC interference group(6.66 vs.41.81,t=69.95,P＜0.01)and G6PD interference group(6.66 vs.43.61,t=48.55,P＜0.01)compared to the control group.The expression of N-Myc downstream regulated gene 1(NDRG1)was higher in the SRC knockdown+G6PD overexpression group than in the G6PD overexpression alone group(0.76 vs.0.48,t=8.55,P＜0.01),while the expression of p-serine/threonine protein kinase(p-Akt)was lower in SRC knockdown+G6PD overexpression group than in G6PD overexpression alone grouo(0.34 vs.0.47,t=4.72,P＜0.01).Conclusion SRC regulated the expression level of NDRG1 by regulating G6PD nuclear translocation and finally played a role in promoting the progression of bladder cancer.
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