Fig. 4

Regulatory mechanisms of A-to-I editing on Alu. The Alu-rich exon on the 3’ end of RHOA mRNA is a target for A-to-I editing, resulting in the production of the RHOAiso2-R176G mutant protein. This mutation enhances RHOA-GTP activity, leading to increased phosphorylation of the ROCK1/2 effector in lung adenocarcinoma (LUAD) cells, which promotes cell proliferation and migration in vitro. In vivo, this modification accelerates tumor growth in xenograft models and drives tumor progression in systemic metastasis models. Additionally, ADAR facilitates immune evasion by modifying Alu elements, thereby disrupting the immunogenicity of their stem-loop structures. This modification prevents recognition by dsRNA sensors such as MDA5, blocking activation of the interferon (IFN) signaling pathway and avoiding apoptosis