MAFF inhibits angiogenesis in non-small cell lung cancer by suppressing YAP1 nuclear translocation.

OBJECTIVE: To investigate the roles of MAFF and Yes-associated protein 1 (YAP1) in regulating angiogenesis in non-small cell lung cancer (NSCLC) and to explore the mechanism through which MAFF inhibits angiogenesis by suppressing YAP1 nuclear translocation. METHODS: Bioinformatics analysis was used to assess MAFF expression and its associated regulatory pathways. Clinical samples from NSCLC patients were analyzed by immunohistochemistry (IHC) to evaluate the correlation between MAFF expression and microvessel density (MVD). Cellular experiments were conducted to examine the effects of MAFF overexpression on proliferation, migration, and angiogenesis. Western blot (WB) and immunofluorescence (IF) analyses were performed to assess the expression of YAP1, vascular endothelial growth factor (VEGF), and connective tissue growth factor (CTGF). Tumor growth suppression was evaluated using nude mouse xenograft models. RESULTS: MAFF was significantly downregulated in NSCLC tissues and correlated with advanced T stage and higher MVD. Overexpression of MAFF inhibited NSCLC cell proliferation, migration, and angiogenesis, and downregulated the expression of YAP1, VEGF, and CTGF. IF confirmed that MAFF suppressed nuclear translocation of YAP1. In vivo, MAFF overexpression reduced tumor volume and weight, which was accompanied by inhibition of the YAP1 signaling pathway. CONCLUSION: MAFF suppresses angiogenesis in NSCLC by blocking YAP1 nuclear translocation and downregulating VEGF and CTGF, highlighting its potential as a therapeutic target.