PIN1 inhibits ferroptosis in gastric cancer cells by regulating the CPEB1‑GPX4 pathway.

Ferroptosis, an iron‑dependent form of programmed cell death, is a promising target for cancer therapy. Peptidyl‑prolyl cis/trans isomerase 1 (PIN1), a member of the peptidyl‑prolyl cis/trans isomerase family, is often overexpressed in cancer and contributes to tumor cell proliferation, survival and metastasis. The present study investigated whether PIN1 regulates ferroptosis in gastric cancer (GC). GC cell models with either PIN1 knockdown or overexpression were established and treated with the ferroptosis inducer erastin, followed by assessment of cell viability and proliferation rate using Cell Couting Kit‑8 and colony formation assays, detection of PIN1 and cytoplasmic polyadenylation element binding protein 1 (CPEB1) expression via western blotting and reverse transcription‑quantitative PCR, and evaluation of glutathione peroxidase 4 (GPX4) expression through immunofluorescence assay. Experimental results indicate that PIN1 depletion increases erastin‑induced ferroptosis, as evidenced by increased levels of reactive oxygen species, malondialdehyde and intracellular free iron. PIN1 overexpression attenuates the erastin‑induced ferroptotic response, as evidenced by decreased levels of ferroptosis‑related biomarkers. Further analysis reveals that silencing PIN1 upregulates CPEB1, which, in turn, suppresses GPX4 expression. Simultaneous knockdown of CPEB1 reverses the ferroptosis‑enhancing effect of PIN1 depletion. These mechanistic findings suggest that PIN1 promotes GPX4 expression by repressing CPEB1, thus inhibiting Erastin‑induced ferroptotic cell death in GC.