文献类型：期刊文献

英文题名：IGF2BP2 regulates gastric cancer radiotherapy resistance through HIF1α-mediated glycolysis

作者：Zhang, Qi[1,3];Liu, Xiaoyu[2];Chen, Yukan[1];Wang, Ruilin[1];Zhao, Shuangyan[1];Tian, Yuting[1];Li, Shuping[4];Liu, Xiaojun[4]

第一作者：Zhang, Qi;张倩;张芹;张茜;张青

通信作者：Li, SP[1];Liu, XJ[1]

机构：[1]Gansu Univ Chinese Med, Clin Med Coll 1, Lanzhou, Gansu, Peoples R China;[2]Lanzhou Univ, Clin Med Coll 1, Lanzhou, Gansu, Peoples R China;[3]Xian Int Med Ctr Hosp, Xian, Shanxi, Peoples R China;[4]Lanzhou Univ, Clin Med Coll 3, Dept Radiat Oncol 2, Lanzhou, Gansu, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Lanzhou Univ, Clin Med Coll 3, Dept Radiat Oncol 2, Lanzhou, Gansu, Peoples R China.

年份：2025

卷号：15

外文期刊名：FRONTIERS IN ONCOLOGY

收录：;Scopus(收录号：2-s2.0-105007417094);WOS:【SCI-EXPANDED(收录号:WOS:001503749000001)】；

基金：The author(s) declare that financial support was received for the research and/or publication of this article. This study was supported by the Natural Science Foundation of Gansu Province (21JR7RA618) and Gansu Provincial People's Hospital Intramural Research Fund Project (20GSSY1-24, 21GSSYA-2).

语种：英文

外文关键词：IGF2BP2; HIF1 alpha; glycolysis; radioresistance; gastric cancer

摘要：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 1 alpha (HIF1 alpha). 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 HIF1 alpha mRNA, positively regulating HIF1 alpha mRNA stability and protein expression in an m6A-dependent manner. High IGF2BP2 expression significantly enhances glycolytic activity in gastric cancer cells, while overexpression of HIF1 alpha partially rescues the suppression of malignant phenotypes caused by IGF2BP2 knockdown, indicating that HIF1 alpha 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.