Cirbp-KO Mouse

Cirbp, also known as cold-inducible RNA-binding protein, is a general stress-response factor in vertebrates. It contains an RNA-recognition motif and a regulatory domain rich in RG/RGG motifs. Cirbp binds to mRNAs under various stress conditions like cold, infections, UV, and hypoxia, regulating mRNA stability and translation. The proteins encoded by its target mRNAs are involved in key cellular pathways such as apoptosis, inflammation, cell proliferation, and translation [6].

In a rat heart transplantation model, Cirbp-KO in young donor hearts led to attenuated hypothermic cardioprotection, while Cirbp overexpression in aged donor hearts improved hypothermic cardioprotection. This indicates that Cirbp is crucial for hypothermic cardioprotection, and its suppression compromises DHODH-mediated ferroptosis defense in aged donor hearts [1]. In nasopharyngeal carcinoma (NPC) cells, Cirbp inhibition enhanced the anti-tumor-killing activity of hyperthermia, while its overexpression induced hyperthermia resistance. ThermomiR-377-3p improved the sensitivity of NPC cells to hyperthermia by suppressing Cirbp expression [2]. CIRBP deficiency in mice was involved in chemotherapy-induced cardiomyocyte apoptosis, and exogenous CIRBP mitigated doxorubicin-induced cardiac apoptosis and dysfunction. CIRBP interacted with OGFR mRNA to repress OGFR expression, conferring myocardium resistance to chemotherapy-induced cardiac apoptosis [3]. In pancreatic cancer, CIRBP acts as a tumor suppressor gene, inducing ferroptosis through the p53/GPX4 pathway to inhibit cell growth [4]. In renal ischaemia-reperfusion injury, CIRBP promoted ferroptosis by interacting with ELAVL1 and activating ferritinophagy. Anti-CIRBP antibody injection in a mouse model of IR inhibited ferroptosis and decreased renal IR injury [5].

In conclusion, Cirbp plays diverse and significant roles in multiple biological processes and diseases. Gene-knockout models, such as in heart transplantation, cancer, and renal injury studies, have revealed that Cirbp is involved in cardioprotection, cancer cell response to hyperthermia and chemotherapy, pancreatic cancer cell ferroptosis, and renal ferroptosis. These findings contribute to understanding the underlying mechanisms of these diseases and may provide potential therapeutic targets.

References:

1. Zhu, Yifan, Jiang, Chenyu, He, Jian, Zhang, Hao, Liu, Yiwei. 2024. Cirbp suppression compromises DHODH-mediated ferroptosis defense and attenuates hypothermic cardioprotection in an aged donor transplantation model. In The Journal of clinical investigation, 134, . doi:10.1172/JCI175645. https://pubmed.ncbi.nlm.nih.gov/38690728/

2. Lin, Tao-Yan, Jia, Jun-Shuang, Luo, Wei-Ren, Xiao, Dong, Sun, Yan. 2024. ThermomiR-377-3p-induced suppression of Cirbp expression is required for effective elimination of cancer cells and cancer stem-like cells by hyperthermia. In Journal of experimental & clinical cancer research : CR, 43, 62. doi:10.1186/s13046-024-02983-3. https://pubmed.ncbi.nlm.nih.gov/38419081/

3. Liu, Cihang, Cheng, Xiaolei, Xing, Junyue, Liu, Lin, Tang, Hao. 2022. CIRBP-OGFR axis safeguards against cardiomyocyte apoptosis and cardiotoxicity induced by chemotherapy. In International journal of biological sciences, 18, 2882-2897. doi:10.7150/ijbs.69655. https://pubmed.ncbi.nlm.nih.gov/35541895/

4. Gao, Hongqiang, Xie, Ran, Huang, Rong, Yang, Qingxiong, Chen, Long. 2022. CIRBP Regulates Pancreatic Cancer Cell Ferroptosis and Growth by Directly Binding to p53. In Journal of immunology research, 2022, 2527210. doi:10.1155/2022/2527210. https://pubmed.ncbi.nlm.nih.gov/36061308/

5. Sui, Mingxing, Xu, Da, Zhao, Wenyu, Zhang, Lei, Zeng, Li. 2021. CIRBP promotes ferroptosis by interacting with ELAVL1 and activating ferritinophagy during renal ischaemia-reperfusion injury. In Journal of cellular and molecular medicine, 25, 6203-16. doi:10.1111/jcmm.16567. https://pubmed.ncbi.nlm.nih.gov/34114349/

6. Corre, Morgane, Lebreton, Alice. 2023. Regulation of cold-inducible RNA-binding protein (CIRBP) in response to cellular stresses. In Biochimie, 217, 3-9. doi:10.1016/j.biochi.2023.04.003. https://pubmed.ncbi.nlm.nih.gov/37037339/