m6A modification enhances the stability of CDC25A promotes tumorigenicity of esophagogastric junction adenocarcinoma via cell cycle.
Int J Biol Sci
; 20(11): 4209-4221, 2024.
Article
em En
| MEDLINE
| ID: mdl-39247830
ABSTRACT
N6-Methyladenosine (m6A) 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 m6A regulator in AEG tumors versus paired normal adjacent tissues from the expression profile of m6A regulators in a large cohort of AEG patients. Silencing IGF2BP3 inhibits AEG progression in vitro and in vivo. By profiling transcriptome-wide targets of IGF2BP3 and the m6A methylome in AEG, we found that IGF2BP3-mediated stabilization and enhanced expression of m6A-modified targets, including targets of the cell cycle pathway, such as CDC25A, CDK4, and E2F1, are critical for AEG progression. Mechanistically, the increased m6A modification of CDC25A 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 m6A/IGF2BP3/CDC25A axis in AEG cells.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Esofágicas
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Adenocarcinoma
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Ciclo Celular
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Adenosina
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Proteínas de Ligação a RNA
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Fosfatases cdc25
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Int J Biol Sci
Assunto da revista:
BIOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Austrália