IRF2-driven upregulation of OAS3 promotes AML cell proliferation by modulating the JAK-STAT signaling pathway.

Acute myeloid leukemia (AML) presents significant treatment challenges due to its heterogeneity and resistance to conventional therapies. This study explored the role of 2'-5'-oligoadenylate synthetase 3 (OAS3) in AML progression and its potential as a prognostic and therapeutic biomarker. Through bioinformatics analysis, OAS3 was found to be significantly upregulated in AML patients and associated with poor clinical outcomes. Functional assays in AML cell lines revealed that silencing OAS3 suppressed cell proliferation, induced G1 phase arrest, and promoted apoptosis, while its overexpression enhanced cell growth. Pathway analysis and western blotting demonstrated that OAS3 regulates the JAK-STAT signaling pathway. Further investigation revealed that interferon regulatory factor 2 (IRF2) acts as a transcription factor that binds to the promoter region of OAS3 and enhances its expression, thereby indirectly modulating the JAK-STAT pathway. Cotransfection experiments with IRF2 and si-OAS3 supported this regulatory mechanism. In vivo studies using a xenograft model and subsequent immunohistochemical analysis of tumor specimens confirmed the role of OAS3 in AML progression. These findings highlight OAS3 as a critical player in AML pathogenesis, functioning through the JAK-STAT pathway activation under the transcriptional control of IRF2. The study suggests that OAS3 could serve as a valuable prognostic marker and therapeutic target, offering a promising avenue to improve AML treatment outcomes.