Fig. 4: CYB5A promotes autophagy by inhibiting the STAT3 signaling pathway.

A The image of phosphorylated protein content determination array (top panel). Core differential proteins were screened by |fold change| > 1.2 of the phosphorylation Ab array (bottom panel). B Western blotting showed that p-STAT3 was the most differentially expressed protein. C Western blot was performed to detect autophagy-related protein expression in HCCLM3 cells. The relative density of each band was analyzed by ImageJ software. D Indicated Cells were exposed to IL-6 (20 ng/mL, 24 h). Whole-cell lysates were analyzed by Western blotting. E Western blot was performed to detect JAK1, JAK2, JAK3, and TYK2 expression in the indicated cells. F Indicated cells were exposed to Hypoxia (20 h). Whole-cell lysates were analyzed by Western blotting. G Typical IF images of CYB5A and p-STAT3 expression in the indicated HCC cell lines. H p-STAT3, LC-3B, and CYB5A levels in lung xenograft tumors were shown by IHC. To prove that CYB5A inhibits STAT3 rather than parallelism, we performed rescue experiments in vitro and in vivo (Supplementary figs. 4–1F and 4–2).