Fig 2: The expression and oncogenic role of JMJD5 in glycolysis and proliferation of GBM. A The localization of HEATR5B-881aa in U251 and U373 cells by IF assays. Green, HEATR5B-881aa; blue, DAPI nuclear staining. Scale bars, 10 µm. B The expression of JMJD5 protein in NBTs, LGGTs, and HGGTs groups. Data are presented as the mean ± SD (n = 9, each group). ***P < 0.001 vs. NBTs group; ###P < 0.001 vs. LGGTs group by one-way ANOVA. C The expression of JMJD5 protein in NHA, U251, and U373 cells. Data are presented as the mean ± SD (n = 3, each group). ***P < 0.001 vs. NHA group by one-way ANOVA. D The effects of JMJD5 on pyruvate kinase enzymatic activity in U251 and U373 cells. E and F The effects of JMJD5 on glucose consumption (E) and lactate production (F) in U251 and U373 cells. G The effects of JMJD5 on ECAR in U251 and U373 cells. H The effects of JMJD5 on proliferation in U251 and U373 cells. Data are presented as the mean ± SD (n = 3, each group). **P < 0.01, ***P < 0.001 vs. sh-JMJD5-NC group; ###P < 0.001 vs. OV-JMJD5-NC group by one-way ANOVA. I The expression of JMJD5 protein in response to HEATR5B-881aa upregulation or downregulation in U251 and U373 cells. Data are presented as the mean ± SD (n = 3, each group). ***P < 0.001 vs. OV-HEATR5B-881aa-NC group; ##P < 0.01 vs. circHEATR5B group by one-way ANOVA. J-L The effects of HEATR5B-881aa and JMJD5 on pyruvate kinase enzymatic activity (J), glucose consumption (K), and lactate production (L) in U251 and U373 cells. M The effects of HEATR5B-881aa and JMJD5 on ECAR in U251 and U373 cells. N The effects of HEATR5B-881aa and JMJD5 on proliferation in U251 and U373 cells. Data are presented as the mean ± SD (n = 3, each group). **P < 0.01, ***P < 0.001 vs. OV-HEATR5B-881aa + OV-JMJD5-NC group by one-way ANOVA

Fig 3: Tumor xenograft studies and mechanism diagram. A Left panel, the nude mice carrying subcutaneous xenografts in different groups and the dissected tumor samples from respective groups. Right panel, subcutaneous tumor growth curves. Data are presented as the mean ± SD (n = 5, each group). ***P < 0.001 vs. OV-NC group; #P < 0.05, ##P < 0.01 vs. OV-ZCRB1+OV-circHEATR5B+OV-HEATR5B-881aa group by two-way ANOVA. B Survival curves of nude mice with orthotopic xenografts (n = 5, each group). C The schematic of the mechanisms of the ZCRB1/circHEATR5B/HEATR5B-881aa/JMJD5/PKM2 pathway in GBM cells