Enhancement of TKI sensitivity in lung adenocarcinoma through m6A-dependent translational repression of Wnt signaling by circ-FBXW7

Abstract

Our bench study, in vivo experiments, and clinical validation have unequivocally shown that circFBXW7 effectively inhibits the abilities of LUAD stem cells and reverses resistance to TKIs by modulating Wnt pathway functions through the action of circFBXW7-185AA on β-catenin ubiquitination and inhibition. The regulatory role of circRNA in Osimertinib treatment has been rarely reported, and our findings reveal that this process operates under the influence of m6A modification. These results highlight the tremendous potential of this approach in enhancing therapeutic strategies and overcoming resistance to multiple TKI treatments.