Casp3, also known as caspase-3, is a major mediator of apoptosis activated during cellular exposure to cytotoxic drugs, radiotherapy, or immunotherapy [3]. It is central to the apoptosis process and is involved in various biological pathways related to programmed cell death. Apoptosis is a crucial biological process for maintaining tissue homeostasis, development, and defense against diseases.

In colon cancer, Casp3 knockout (KO) HCT116 cells were less clonogenic, invasive, and more sensitive to radiation and mitomycin C in vitro. In vivo, CASP3KO cells formed tumors at similar rates but were more sensitive to radiotherapy and less prone to pulmonary metastasis. The KO cells also showed reduced epithelial-mesenchymal transition (EMT) phenotypes compared to parental cells [3].

In epithelial cells, occludin down-regulation reduces Caspase-3 expression, limiting apoptosis and contributing to mucosal homeostasis in inflammatory conditions [1]. In periodontitis, the rs4647602 GG genotype of CASP3 is associated with an increased risk in South Indians of Tamil ethnicity [2].

In breast cancer cells, caspase-3 mediates GSDME-induced pyroptosis through the ROS/JNK signalling pathway [4]. In recurrent miscarriage, natural killer cells may contribute to the condition through the SP1-CASP3-PARP1 pathway [5]. In osteoarthritis, miR-98-5p protects chondrocytes from IL-1β-induced damage by targeting CASP3 [6].

In conclusion, Casp3 plays a vital role in apoptosis and is involved in multiple disease conditions such as cancer, inflammatory bowel disease, periodontitis, recurrent miscarriage, and osteoarthritis. The use of Casp3 KO models has been instrumental in revealing its functions in these diseases, helping to understand the underlying mechanisms and potentially providing new therapeutic targets.