Oas3, short for 2'-5'-oligoadenylate synthetase 3, is an enzyme induced by interferons and belongs to the 2', 5' oligoadenylate synthase family. It activates potential RNA enzymes to degrade viral mRNA, inhibit viral protein synthesis, and promote apoptosis in virus-infected cells. Oas3 is involved in the IFN-β1b/JAK/STAT1 pathway and the OAS-RNase L antiviral pathway [2,5]. It is also associated with the tumor microenvironment, disease staging, prognosis, and treatment response in multiple cancer types [3].

In sepsis-induced acute lung injury (SALI), downregulation of E3 ligase TRIM21 leads to Oas3 deubiquitination at the K1079 site in lung epithelial cells. This increases Oas3 protein level in a proteasomal-dependent manner, promoting epithelial cell apoptosis through its downstream effector molecule, RNase L, and driving SALI [1]. In pancreatic cancer, Oas3 is upregulated by pancreatic cancer cells via the lactate/METTL3/OAS3 axis. Oas3 in macrophages is essential for M2d polarization, and its deficiency impairs M2d polarization and pro-tumor functions, enhancing the efficacy of gemcitabine and anti-PD-L1 mAb in humanized mouse models [4].

In conclusion, Oas3 is crucial in antiviral defense, apoptosis regulation, and tumor-related processes. Studies using mouse models in SALI and pancreatic cancer have revealed its role in disease development, providing potential therapeutic targets for these diseases.