Ireb2, also known as iron-responsive element binding protein 2, is a key regulator in iron metabolism. It binds to iron-responsive elements (IREs) in the untranslated regions of mRNAs involved in iron metabolism, thereby regulating the translation or stability of these mRNAs. This regulation is crucial for maintaining cellular iron homeostasis, which impacts various biological processes and is associated with multiple diseases [2,3,4,5,6].

In chronic obstructive pulmonary disease (COPD), m6A-modified circSAV1 forms an RNA-protein ternary complex with YTHDF1 and Ireb2 mRNA, facilitating the translation of Ireb2. Elevated Ireb2 protein levels disrupt iron homeostasis, leading to the accumulation of a labile iron pool and lipid peroxidation, which triggers ferroptosis in lung epithelial cells. Silencing circSAV1 or treating with deferoxamine blocks CS-induced ferroptosis of lung epithelial cells, attenuating COPD progression in mice [1]. In non-small-cell lung cancer, knockdown of Ireb2 notably weakens curcumin-induced anti-tumor effect and ferroptosis, suggesting Ireb2 is involved in curcumin-induced ferroptosis [4]. In colorectal cancer cells, miR-19a suppresses ferroptosis by negatively regulating Ireb2, as Ireb2 is a direct target of miR-19a [7].

In conclusion, Ireb2 is essential for maintaining iron homeostasis. Model-based research, especially in the context of COPD, non-small-cell lung cancer, and colorectal cancer, has revealed its role in ferroptosis-related disease mechanisms. Understanding Ireb2's function provides insights into the pathogenesis of these diseases and may offer potential therapeutic targets.