METTL7A drives pituitary neuroendocrine tumor invasion via an m6A-dependent epigenetic mechanism upregulating EGFR/PI3K/Akt signaling

Background Pituitary neuroendocrine tumors (PitNETs) are among the most prevalent primary central nervous system neoplasms. While most are benign, a subset exhibits aggressive growth and high recurrence rates with limited treatment options. This study investigated the role of METTL7A, an m6A methyltransferase, in PitNET invasion through integrated bioinformatic and functional analyses. Methods Public transcriptomic GEO datasets (GSE26048 and GSE51618) were analyzed to identify differentially expressed genes (DEGs) between invasive and non-invasive pituitary neuroendocrine tumor. Overlapping DEGs were subjected to KEGG pathway enrichment analysis, and METTL7A and EGFR were identified as key invasion-associated candidates. This study employed genetically modified human PA cell models combined with RNA immunoprecipitation (RIP), transcriptional inhibition assays, and functional analyses (including proliferation, migration, and invasion assays) to investigate the role of the RNA m 6 A methyltransferase METTL7A. Functional rescue experiments were performed using EGFR knockdown and pharmacological inhibition of PI3K with the specific inhibitor LY294002. Results From the two GEO datasets, the integrated analysis turned out 755 overlapping DEGs existing between invasive and non-invasive pituitary neuroendocrine tumor. KEGG enriched with high in PI3K-Akt, cAMP, Rap1 signaling. METTL7A and EGFR were consistently upregulated in invasive tumors and positively correlated. METTL7A regulates EGFR expression and its pro-invasive functions through a previously unrecognized mechanism. METTL7A significantly enhances EGFR mRNA stability (p < 0.001) via m 6 A modification, thereby activating the PI3K/Akt signaling pathway. This activation stimulates tumor cell proliferation (1.7-2.0-fold increase in viability in overexpression groups), migration, and invasion (p < 0.001). Both EGFR knockdown and pharmacological PI3K inhibition with LY294002 markedly attenuated the METTL7A-mediated oncogenic effects (p < 0.05). Conclusion METTL7A as the first identified m 6 A-dependent regulator of the EGFR/PI3K/Akt signaling axis in pituitary neuroendocrine tumor. This discovery advances the mechanistic understanding of PA invasion and provides a molecular basis for developing novel epigenetic intervention strategies targeting METTL7A or m 6 A modification.