Casp3, also known as caspase-3, is a major mediator of apoptosis activated during cellular exposure to cytotoxic drugs, radiotherapy or immunotherapy [2]. It is central to apoptosis and is involved in multiple biological processes. Casp3 activation leads to the cleavage of various cellular substrates, driving the apoptotic process. It also participates in non-apoptotic roles such as influencing tumor relapse and angiogenesis [2].

In a study of periodontitis, the rs4647602 GG genotype of CASP3 was associated with an increased periodontitis risk in South Indians of Tamil ethnicity, suggesting a role of Casp3 gene polymorphism in periodontal disease pathogenesis [1]. In colon cancer cell lines, Casp3 knockout (KO) HCT116 cells were less clonogenic, invasive, and more sensitive to radiation and mitomycin C, and less prone to pulmonary metastasis in vivo, indicating that Casp3 regulates the migration, invasion and metastasis of colon cancer cells [2]. In breast cancer cells, caspase-3-mediated GSDME induced pyroptosis through the ROS/JNK signalling pathway [3]. In chondrocytes related to osteoarthritis, miR-98-5p played suppressive effects on IL-1β-induced injury by targeting CASP3 [4].

In conclusion, Casp3 is a crucial regulator in apoptosis and has diverse roles in multiple diseases including periodontitis, colon cancer, breast cancer, and osteoarthritis. Gene knockout models, such as the Casp3 KO in colon cancer cells, have been instrumental in revealing its functions in disease-related biological processes, helping to understand disease mechanisms and potentially guiding new therapeutic strategies.

References:

1. Loka, Arya Mitra, Ponnaiyan, Deepa, Parthasarathy, Harinath, Tadepalli, Anupama, Victor, Dhayanand John. 2022. Association of the CASP3 rs4647602 Gene Polymorphism with Periodontitis in South Indians of Tamil Ethnicity. In Genetic testing and molecular biomarkers, 26, 391-397. doi:10.1089/gtmb.2022.0018. https://pubmed.ncbi.nlm.nih.gov/35976099/

2. Zhou, Min, Liu, Xinjian, Li, Zonghai, Li, Fang, Li, Chuan-Yuan. 2018. Caspase-3 regulates the migration, invasion and metastasis of colon cancer cells. In International journal of cancer, 143, 921-930. doi:10.1002/ijc.31374. https://pubmed.ncbi.nlm.nih.gov/29524226/

3. Zhang, Ziwen, Zhang, Han, Li, Dongbo, Qin, Qi, Zhang, Qingyuan. 2021. Caspase-3-mediated GSDME induced Pyroptosis in breast cancer cells through the ROS/JNK signalling pathway. In Journal of cellular and molecular medicine, 25, 8159-8168. doi:10.1111/jcmm.16574. https://pubmed.ncbi.nlm.nih.gov/34369076/

4. Lv, Hang, Liu, Peiran, Hu, Hai, Li, Xiaodong, Li, Pengfei. 2024. MiR-98-5p plays suppressive effects on IL-1β-induced chondrocyte injury associated with osteoarthritis by targeting CASP3. In Journal of orthopaedic surgery and research, 19, 239. doi:10.1186/s13018-024-04628-9. https://pubmed.ncbi.nlm.nih.gov/38615043/