METTL3-mediated m6A methylation of LncRNA DUXAP8 promoted esophageal squamous cell carcinoma progression by activating the PI3K/AKT signaling pathway

To uncover the mechanism of METTL3 and LncRNA DUXAP8 in esophageal squamous cell carcinoma (ESCC) progression. LncRNA DUXAP8 expression was assessed by qRT-PCR. Its overexpression and knockdown in ESCC cells were evaluated for effects on viability and metastasis. WB analyzed PI3K/AKT signaling proteins. MeRIP and RIP assays explored METTL3-DUXAP8 interaction and m6A methylation. In vivo experiments validated the mechanism. DUXAP8 was upregulated in ESCC and enhanced cell proliferation, metastasis, and PI3K/AKT activation. It was confirmed that METTL3-DUXAP8 interaction and METTL3 mediated the m6A methylation of DUXAP8. The total level of DUXAP8 and its m6A methylation in TE-1 and KSYE-150 cell lines was decreased significantly by METTL3 knockdown, which inactivated the PI3K/AKT pathway and reduced cell proliferation and metastasis. Xenograft tumor mouse model confirmed that si-METTL3 can reverse DUXAP8-mediated ESCC proliferation via activating the PI3K/AKT pathway. METTL3 drives ESCC oncogenesis by binding and positively regulating DUXAP8 in an m6A-dependent manner and activating the PI3K/AKT pathway.