Casp8, short for caspase-8, apoptosis-related cysteine peptidase, is a key enzyme in the apoptosis pathway. It is essential for regulating cell death and is involved in various biological processes. Apoptosis is a fundamental cellular mechanism that helps maintain tissue homeostasis, and Casp8's role in this pathway makes it biologically significant. Genetic models, such as KO/CKO mouse models, can be valuable for studying its functions [5].

In neuroblastoma, methylation of CASP8 is associated with poor prognosis, with the five-year survival for the methylated arm being lower compared to the unmethylated arm [1]. In traumatic brain injury, CASP8 may be a potential therapeutic target as it is correlated with pyroptosis [2]. For neural tube defects, Casp8 hypomethylation is associated with their formation, potentially induced by oxidative stress from polycyclic aromatic hydrocarbon exposure [3]. In prostate cancer, high levels of CASP8 were detected in pre-operative serum samples, and its mRNA expression was upregulated in cancer tissues, suggesting it may be a biomarker for high-risk prostate cancer [4]. A meta-analysis showed that some CASP8 polymorphisms reduce cancer risk, while others increase it [5]. In K-562 cells, circRNA.0007127 regulates apoptosis through the miR-513a-5p/CASP8 axis [6]. In renal cell carcinoma, CASP8 is an autophagy-pyroptosis-related gene, highly expressed in tumor tissues, associated with higher pathological staging and poorer prognosis [7]. In neuroblastoma patients, low expression of CASP8 is associated with MYCN amplification and has prognostic value [8].

In conclusion, Casp8 plays a crucial role in apoptosis and is associated with various diseases, including neuroblastoma, traumatic brain injury, neural tube defects, prostate cancer, and renal cell carcinoma. Studies using different models, though not specifically KO/CKO mouse models in all cases, have provided insights into its functions in these disease conditions, helping to understand the underlying mechanisms and potentially identify new treatment strategies.

References:

1. Hassan, Waleed M, Bakry, Mohamed S, Siepmann, Timo, Illigens, Ben. 2020. Association of RASSF1A, DCR2, and CASP8 Methylation with Survival in Neuroblastoma: A Pooled Analysis Using Reconstructed Individual Patient Data. In BioMed research international, 2020, 7390473. doi:10.1155/2020/7390473. https://pubmed.ncbi.nlm.nih.gov/33381579/

2. Zhao, Gengshui, Fu, Yongqi, Yang, Chao, Yang, Xuehui, Hu, Xiaoxiao. 2023. CASP8 Is a Potential Therapeutic Target and Is Correlated with Pyroptosis in Traumatic Brain Injury. In World neurosurgery, 174, e103-e117. doi:10.1016/j.wneu.2023.03.004. https://pubmed.ncbi.nlm.nih.gov/36894003/

3. Huang, Yun, Ren, Aiguo, Wang, Linlin, Li, Zhiwen, McDonald, Jasmine A. 2019. Casp8 hypomethylation and neural tube defects in association with polycyclic aromatic hydrocarbon exposure. In Clinical epigenetics, 11, 72. doi:10.1186/s13148-019-0673-6. https://pubmed.ncbi.nlm.nih.gov/31064411/

4. Liu, Shiqin, Garcia-Marques, Fernando, Zhang, Chiyuan Amy, Brooks, James D, Stoyanova, Tanya. 2021. Discovery of CASP8 as a potential biomarker for high-risk prostate cancer through a high-multiplex immunoassay. In Scientific reports, 11, 7612. doi:10.1038/s41598-021-87155-5. https://pubmed.ncbi.nlm.nih.gov/33828176/

5. Hashemi, Mohammad, Aftabi, Sajjad, Moazeni-Roodi, Abdolkarim, Wiechec, Emilia, Ghavami, Saeid. 2020. Association of CASP8 polymorphisms and cancer susceptibility: A meta-analysis. In European journal of pharmacology, 881, 173201. doi:10.1016/j.ejphar.2020.173201. https://pubmed.ncbi.nlm.nih.gov/32442541/

6. Li, Xiajing, Zhang, Yiyu, Wang, Ning, Duan, Yuyou, Wei, Yaming. . CircRNA.0007127 triggers apoptosis through the miR-513a-5p/CASP8 axis in K-562 cells. In Journal of Zhejiang University. Science. B, 23, 732-746. doi:10.1631/jzus.B2200048. https://pubmed.ncbi.nlm.nih.gov/36111570/

7. Li, Tao, Liu, Ning, Zhang, Guangyuan, Chen, Ming. . CASP4 and CASP8 as newly defined autophagy-pyroptosis-related genes associated with clinical and prognostic features of renal cell carcinoma. In Journal of cancer research and therapeutics, 18, 1952-1960. doi:10.4103/jcrt.jcrt_126_22. https://pubmed.ncbi.nlm.nih.gov/36647955/

8. Altun, Zekiye, Ceyhan, Metin, Yuan, Hongling, Aktaş, Safiye, Olgun, Nur. 2024. Low Expression of CASP8 Could be a Prognostic Biomarker in Neuroblastoma Patients. In Journal of child neurology, 39, 386-394. doi:10.1177/08830738241273431. https://pubmed.ncbi.nlm.nih.gov/39234689/