ADAR1 is required for acute myeloid leukemia cell survival by modulating post-transcriptional Wnt signaling through impairing miRNA biogenesis.

Recent extensive studies on the genomic and molecular profiles of acute myeloid leukemia (AML) have expanded the treatment options, including, a range of compounds represented by fms-like tyrosine kinase 3 and isocitrate dehydrogenase 1/2 inhibitors. However, despite this progress, further treatments for AML are still required. Adenosine deaminase acting on RNA 1 (ADAR1) has been shown to play an important oncogenic role in many cancers, but its involvement in AML progression remains underexplored. In this study, we demonstrated that ADAR1 was overexpressed in AML and served as a crucial oncogenic target. Loss of ADAR1 inhibited the Wnt signaling pathway, blocked AML cell proliferation, and induced apoptosis. Importantly, we demonstrate that ADAR1, as an RNA-binding protein, interacts with pri-miR-766 independently of its editing function, regulating the maturation of miR-766-3p and enhancing the expression of WNT5B. Genetic inhibition or use of the ADAR1 inhibitor ZYS-1 significantly suppressed AML cell growth both in vitro and in vivo. Overall, these results elucidated the tumorigenic mechanism of ADAR1 and validated it as a potential drug target in AML.