Fig 2: The knockdown of COX4I2 in NIH3T3 cell line resulted in changes of angiogenesis-related factors. (A) Changes of COX4I2 mRNA in NIH3T3 cell line after interference of three targets. (B) Changes of angiogenesis-related factors VEGFA, ANG1, ANG2 and HGF mRNA in NIH3T3 cell line after COX4I2 knockdown. (NS: No Significance; *: P<0.05; **: P<0.01; ***: P<0.001).

Fig 3: Effect of CPZ on cell cycle(A–D) Average distributions of cells in G1, S, and G2/M phases for TMZ-sensitive U251 glioma cells (A), TMZ-resistant UTMZ glioma cells (B), and U251 glioma cells with CcO expressing COX4-2 (C) or COX4-1 (D). Cells were exposed to 0, 10, or 20 µM CPZ for 24 h. Results represent the average from two independent experiments.

Fig 4: Single cell atlas of pheochromocytoma. (A) Two-dimensional t-SNE clustering analysis showed that the cells were divided into 21 clusters and labeled with different colors. (B, C) The expression of TH and CHGA genes was used to identify pheochromocytoma tumor cells. (D) The expression of PTPRC gene was used to identify immune cells. (E–G) The expression of VWF, PECAM1 and PLVAP genes was used to identify endothelial cells. (H, I) The expression of ACTA2 and PDGFRB genes was used to identify fibroblasts. (J) Location and expression of COX4I2 gene in all cells.

Fig 5: Survival data for CPZ-treated and untreated glioma-bearing mice(A) Representative Western blot showing the expression of COX4-1 and COX4-2 isoforms in CcO from TMZ-resistant UTMZ or TMZ-sensitive U251 cells. (B) Quantitative analysis of the relative expression levels of COX4-1 and COX4-2 isoforms in CcO from U251 and UTMZ cells. Results represent the average from duplicate determinations. (C, D) TMZ-resistant UTMZ (C) or TMZ-sensitive U251 (D) glioma-bearing mice were treated with CPZ (5 or 7 mg/kg) or with saline (vehicle) as a control (n = 10 mice/group). In mice bearing UTMZ tumors, CPZ treatment significantly improved survival (***p = 0.0007 versus saline). In mice bearing U251 tumors, there was no significant difference in survival between CPZ-treated and saline-treated controls (p = 0.377).