Fig. 4: NEK6 modulation of C-MYC protein regulates de novo purine synthesis and chemoresistance.

A Changes in C-MYC protein levels in NCI/ADR-RES and SKOV3/DDP cells after 10058-F4 (8 µM) treatment. N = 3. Data presented as mean ± SD. *P < 0.05; Student’s t-test. B Changes in mRNA levels of de novo purine synthesis-related enzymes after 10058-F4 treatment. N = 5. Data presented as mean ± SD. *P < 0.05; **P < 0.01; ***P < 0.001; ANOVA. C Representative images of purine bodies in cells after 10058-F4 intervention. D Quantification of purinosomes. N = 5. Data presented as mean ± SD. ***P < 0.001; ANOVA. E Impact of 10058-F4 and subsequent purine supplementation on cell proliferation based on EDU detection. N = 5. Data presented as mean ± SD. *P < 0.05; **P < 0.01; ns, not significant; ANOVA. F Flow cytometry detection of the influence of 10058-F4 and subsequent purine supplementation on intracellular DOX uptake. N = 3. Data presented as mean ± SD. *P < 0.05; ***P < 0.001; ANOVA. G Flow cytometry detection of the effect of 10058-F4 and subsequent purine supplementation on DOX-induced cell apoptosis. H Protein expression levels after NEK6 knockdown and C-MYC introduction. N = 3. Data presented as mean ± SD. **P < 0.01; ***P < 0.001 ns, not significant; ANOVA. I Heatmap of normalized abundance of purine metabolites after NEK6 knockdown and C-MYC introduction. N = 6. J Relative abundance of purine intermediates. N = 6. Data presented as mean ± SD. *P < 0.05; **P < 0.01; ***P < 0.001; ANOVA.