Fig. 4

Overexpression of YY1 inhibits GC cell ferroptosis and mediates Apatinib-resistance via the p53 signaling pathway. (A) Luciferase reporter assay showed that Transferrin was transcriptionally regulated by YY1(*p < 0.05, t-test). (B)Western blot demonstrated that Transferrin expression was upregulated after YY1 overexpression. (C) Protein levels of p53 decreased after YY1 overexpression, furthermore SLC7A11 was upregulated, indicates YY1 inhibits gastric cancer via the p53 manner. Moreover, TFR1 was downregulated which might further inhibit GC cell ferroptosis. (D-E) YY1-overexpressed and YY1-overexpressed with SLC7A11 knock down HGC-27 and MFC cells were treated with Erastin in vitro. The cell death rate (D) and relative MDA levels (E) showed that YY1 overexpression could inhibit GC cell ferroptosis (*p < 0.05, ANOVA). (F-G) Relative intro-cellular Fe²⁺(F) and level intro-cellular GSH (G) level in YY1-overexpressed and YY1-overexpressed with SLC7A11 knock down HGC-27 and MFC cells (*p < 0.05, ANOVA). (H) YY1-overexpressed HGC-27 and MFC cells developed ferroptosis thus Apatinib drug resistance in vitro (*p < 0.05, ANOVA)