mA modification enhances the stability of promotes tumorigenicity of esophagogastric junction adenocarcinoma via cell cycle.

6-Methyladenosine (mA) modification and its regulators play critical roles in human cancers, but their functions and regulatory mechanisms in adenocarcinoma of the esophagogastric junction (AEG) remain unclear. Here, we identified that IGF2BP3 is the most significantly up-regulated mA regulator in AEG tumors versus paired normal adjacent tissues from the expression profile of mA regulators in a large cohort of AEG patients. Silencing IGF2BP3 inhibits AEG progression and . By profiling transcriptome-wide targets of IGF2BP3 and the mA methylome in AEG, we found that IGF2BP3-mediated stabilization and enhanced expression of mA-modified targets, including targets of the cell cycle pathway, such as , , and , are critical for AEG progression. Mechanistically, the increased mA modification of accelerates the G1-S transition. Clinically, up-regulated IGF2BP3, METTL3, and CDC25A show a strong positive correlation in TCGA pan-cancer, including AEG. In conclusion, our study highlights the role of post-transcriptional regulation in modulating AEG tumor progression and elucidates the functional importance of the mA/IGF2BP3/CDC25A axis in AEG cells.