IREB2 overexpression inhibited the malignant progression of cervical cancer by inducing ferroptosis

Background Ferroptosis is an iron-dependent form of regulated cell death driven by lipid peroxidation and has shown potential relevance in cancer therapy. Iron-responsive element-binding protein 2 ( IREB2 ) is a crucial regulator of cellular iron metabolism and has been implicated in ferroptosis regulation. However, the role of IREB2 in cervical cancer (CC) remains unclear. Methods IREB2 expression was measured in CC tissues and cell lines. Gain-of-function assays were performed to evaluate the effects of IREB2 overexpression on the proliferation, migration, invasion of CC cells, and ferroptosis-related changes. The involvement of ferroptosis was further assessed using the ferroptosis inhibitor ferrostatin-1 (Fer-1). A xenograft tumor model was used to examine the effect of IREB2 overexpression on tumor growth in vivo . Results IREB2 expression was downregulated in CC tissues and cell lines. IREB2 overexpression suppressed CC cell proliferation, migration and invasion. In addition, IREB2 overexpression decreased GPX4 and GSH levels and increased ROS, MDA and Fe 2+ levels, indicating enhanced ferroptosis. Fer-1 treatment partially reversed the inhibitory effects of IREB2 overexpression on the malignant phenotypes of CC cells. In vivo, IREB2 overexpression suppressed xenograft tumor growth, and this effect was partly attenuated by Fer-1 treatment. Conclusion IREB2 was downregulated in CC, and its overexpression inhibited malignant progression of CC by promoting ferroptosis. These findings suggested that IREB2 may be involved in ferroptosis-mediated regulation of CC progression, providing a potential molecular direction for further investigation.