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ORIGINAL RESEARCH article
Front. Oncol.
Sec. Gastrointestinal Cancers: Gastric and Esophageal Cancers
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1512177
IGF2BP2 Regulates Gastric Cancer Radiotherapy Resistance Through HIF1α-Mediated Glycolysis
Provisionally accepted- 1The First Clinical Medical College, Gansu University of Chinese Medicine, Lanzhou, Gansu Province, China
- 2Gansu Provincial Hospital, Lanzhou, Gansu Province, China
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This study reveals the core mechanism by which insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) drives tumor progression and radiotherapy resistance in gastric cancer (GC) through m6A-dependent regulation of hypoxia-inducible factor 1α (HIF1α). Clinical analyses show that IGF2BP2 is significantly overexpressed in gastric cancer tissues, and its expression level is closely associated with tumor size and poor patient prognosis. Functional studies demonstrate that elevated expression of IGF2BP2 accelerates the transition of gastric cancer cells from the G1 phase to the G2/M phase of the cell cycle and markedly enhances cell proliferation and migration through anti-apoptotic effects. Mechanistically, IGF2BP2 specifically binds to the m6A-modified "GGACU" motif within the coding region of HIF1α mRNA, positively regulating HIF1α mRNA stability and protein expression in an m6A-dependent manner. High IGF2BP2 expression significantly enhances glycolytic activity in gastric cancer cells, while overexpression of HIF1α partially rescues the suppression of malignant phenotypes caused by IGF2BP2 knockdown, indicating that HIF1α serves as a key downstream effector mediating the oncogenic role of IGF2BP2 in gastric cancer. Furthermore, knockdown of IGF2BP2 significantly increases radiosensitivity by exacerbating DNA damage and enhancing oxidative stress.
Keywords: IGF2BP2, HIF1α, Glycolysis, radioresistance, gastric cancer
Received: 16 Oct 2024; Accepted: 07 Apr 2025.
Copyright: © 2025 Zhang, Wang, Tian, Chen, Zhao, Wang, Liu and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
XJ Liu, Gansu Provincial Hospital, Lanzhou, 730000, Gansu Province, China
Shuping Li, Gansu Provincial Hospital, Lanzhou, 730000, Gansu Province, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.