Chidamide, a histone deacetylase inhibitor with established anti-tumor properties, requires further investigation regarding its specific impact on lung cancer progression. Our results showed that chidamide treatment significantly inhibited proliferation, migration, and invasion of non-small cell lung cancer (NSCLC) cells while inducing apoptosis. The treatment with chidamide also downregulated methyltransferase 3 (METTL3), the catalytic subunit of the N6-adenosine-methyltransferase complex, in A549 and H1299 cells. Overexpression of METTL3 reversed the inhibitory effects of chidamide on NSCLC cell progression. Furthermore, we found that METTL3 stabilized EPH receptor A7 (EPHA7) expression through an m6A-dependent mechanism. Conversely, overexpression of EPHA7 counteracted the effects of METTL3 silencing or chidamide treatment in both cell lines. In vivo, chidamide treatment reduced EPHA7 protein expression by regulating METTL3, leading to inhibited tumor growth. Collectively, these findings identified the METTL3/EPHA7 axis as a key mediator of chidamide's anti-tumor effects, suggesting chidamide's potential as a novel therapeutic strategy for NSCLC.
Keywords: EPHA7; METTL3; NSCLC; chidamide.