Polystyrene microspheres could inhibit the ferroptosis of prostate cancer cells via USP39/IGF2BP3/MAPK4 axis.

BACKGROUND: Polystyrene (PS) particles, which have been recognized as emerging environmental pollutants, have increasingly been associated with various human diseases. However, their specific role and underlying mechanisms in prostate cancer development have not been fully elucidated. METHODS: We investigated the characterization properties of PS particles. Subsequently, we examined the impact of PS particles on prostate cancer proliferation using in vitro experiments. Through mRNA sequencing, RIP, and mass spectrometry analysis, we confirmed a close interaction among USP39, IGF2BP3, and MAPK4. The rescue experiment demonstrated that ferroptosis is intricately involved in this process. To further validate our results, we performed mouse xenograft experiments. RESULTS: In this study, PS particles significantly enhanced the proliferation, migration, and invasion of prostate cancer cells through the regulation of ferroptosis. It was found that USP39 interacts with IGF2BP3, which, in turn, stabilizes MAPK4, a key regulator of ferroptosis. CONCLUSIONS: These findings illuminate the complex relationship between environmental pollutants such as PS and cancer progression, offering new avenues for research and potential therapeutic interventions in prostate cancer.