LincNEAT1 Encoded‐NEAT1‐31 Promotes Phagocytosis by Directly Activating the Aurora‐A–PI3K–AKT Pathway

Abstract Macrophages play vital roles in innate and adaptive immunity, and their essential functions are mediated by phagocytosis and antigen presentation. Long non‐coding ribonucleic acid nuclear enriched abundant transcript 1 ( LincNEAT1 ) is specifically translated during phagocytosis. Great efforts have been made to explore the potential mechanisms of action of these phagocytic checkpoints. However, the use of a systematic checkpoint scanning strategy has been far from satisfactory, and intrinsic phagocytic activators have not been fully elucidated. Therefore, in vitro phagocytosis assays are performed using primary healthy donor macrophages and breast cancer cells. An equal number of cells are subjected to ribosome profiling, and immune system‐specific phagocytic activators are identified. LincNEAT1 and encoded micro peptide NEAT1‐31, are considerably upregulated in phagocytic macrophages. Moreover, purified NEAT1‐31 promoted the phagocytosis of multiple cancer cell‐types. Phosphoproteomic analysis reveals that NEAT1‐31 directly promoted Aurora‐A activity and activated phosphatidylinositol 3‐kinase/protein kinase B signaling. NEAT1‐31 enhanced the efficacy of anti‐CD47 in vivo and in vitro. Thus, the study identified a novel protein drug that can directly enhance the phagocytic function, thereby providing a new option for immunotherapy.