Cirbp, also known as cold-inducible RNA-binding protein, is a general stress-response factor in vertebrates. It has an RNA-recognition motif and a regulatory domain rich in RG/RGG motifs. Cirbp binds mRNAs under various stress conditions (such as cold, infections, UV, hypoxia) and regulates their stability and translation. The proteins encoded by its target mRNAs are involved in key stress-responsive cellular pathways like apoptosis, inflammation, cell proliferation, and translation [4].

In a rat heart transplantation model, Cirbp-KO rats' young donor hearts showed attenuated hypothermic cardioprotection, indicating Cirbp's role in this process. Aged donor hearts with decreased Cirbp expression had severe ferroptosis after transplantation, and restoring Cirbp expression improved hypothermic cardioprotection. The mechanism involves Cirbp's regulation of dihydroorotate dehydrogenase (DHODH) expression, which affects ubiquinone reduction, lipid peroxidation, and ferroptosis [1]. In nasopharyngeal carcinoma cells, Cirbp inhibition enhanced the anti-tumor-killing activity of hyperthermia, while overexpression induced hyperthermia resistance. ThermomiR-377-3p improved hyperthermia sensitivity by suppressing Cirbp expression, and Cirbp affected DNA damage repair, stemness, and apoptosis [2]. CIRBP deficiency in cardiomyocytes led to increased apoptosis induced by diverse chemotherapeutic agents, and exogenous CIRBP mitigated doxorubicin-induced cardiac apoptosis and dysfunction by repressing OGFR [3].

In conclusion, Cirbp plays crucial roles in multiple biological processes, especially in stress-related responses. Gene knockout models, like the Cirbp-KO rat in heart transplantation studies, have revealed its importance in hypothermic cardioprotection, hyperthermia response in cancer cells, and chemotherapy-induced cardiotoxicity. These findings provide insights into potential therapeutic strategies for heart transplantation, cancer treatment, and protection against chemotherapy-related heart damage.