m 6 A modification enhances the stability of CDC25A promotes tumorigenicity of esophagogastric junction adenocarcinoma via cell cycle.
| Autor: | Pan Y; Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.; Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China.; Zhongda Hospital, School of Life Sciences and Technology, Advanced Institute for Life and Health, Southeast University, Nanjing 210096, China., Feng H; Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China., Zhou J; Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China., Zhang W; Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China., Liu Y; Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China., Zheng J; Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China., Wang J; Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China., Gao S; Zhongda Hospital, School of Life Sciences and Technology, Advanced Institute for Life and Health, Southeast University, Nanjing 210096, China., Li Y; Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China. |
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| Jazyk: | angličtina |
| Zdroj: | International journal of biological sciences [Int J Biol Sci] 2024 Aug 06; Vol. 20 (11), pp. 4209-4221. Date of Electronic Publication: 2024 Aug 06 (Print Publication: 2024). |
| DOI: | 10.7150/ijbs.98535 |
| Abstrakt: | N 6-Methyladenosine (m 6 A) 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 m 6 A regulator in AEG tumors versus paired normal adjacent tissues from the expression profile of m 6 A 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 m 6 A methylome in AEG, we found that IGF2BP3-mediated stabilization and enhanced expression of m 6 A-modified targets, including targets of the cell cycle pathway, such as CDC25A , CDK4 , and E2F1 , are critical for AEG progression. Mechanistically, the increased m 6 A 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 m 6 A/IGF2BP3/CDC25A axis in AEG cells. Competing Interests: Competing Interests: The authors have declared that no competing interest exists. (© The author(s).) |
| Databáze: | MEDLINE |
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