Fig. 5: POLQ stimulates DHODH expression via the transcription factors E2F4.

A Venn diagram showing a mode for screening the putative upstream TFs of DHODH. B Public database [https://depmap.org/portal/] correlation analysis in cell lines (n = 84) between E2F4, POLQ, and DHODH. Significance was evaluated by Pearson correlation. C, D The mRNA and protein levels of E2F4 were detected in control and POLQ- knockdown cell lines. E, F The mRNA and protein levels of E2F4 and DHODH were detected in control and E2F4- knockdown cell lines. G, H The mRNA and protein levels of DHODH were detected in control and E2F4 overexpression cell lines. I DHODH transcription activity was examined by luciferase assay. J ChIP results of E2F4 binding on DHODH promoter in MGC-803 cells, primers were designed based on E2F4 binding peak regions depicted in the JASPAR database. K High E2F4 expression correlates with resistance to ferroptosis inducers (RSL3, ML162, and ML210) in cancer cells. Plotted data were mined from the CTRP database. L Protein expression levels in E2F4- knockdown cells overexpressing DHODH. M Cell viability in control (Si NC), E2F4 knockdown (Si E2F4), and Si E2F4 + DHODH cells treated with RSL3 (10 µM) or erastin (15 µM) for 24 h. N Respective lipid peroxidation levels were assessed and calculated by flow cytometry using BODIPY C11. O Cell viability in control (ShNC), POLQ knockdown (ShPOLQ), and ShPOLQ + E2F4 cells treated with RSL3 (10 µM) or erastin (15 µM) for 24 h.