The m6A reader IGF2BP2 promotes pancreatic cancer progression through the m6A-SLC1A5-mTORC1 axis

作者：Xi Pu, Yuting Wu, Weiguo Long, Xinyu Sun, Xiao Yuan, Deqiang Wang, Xu Wang, Min Xu · 发表于：Cancer Cell International · 年份：2025 · DOI：10.1186/s12935-025-03736-8 · 被引用次数：8 · 研究领域：RNA modifications and cancer、Cancer, Hypoxia, and Metabolism、Metalloenzymes and iron-sulfur proteins

BACKGROUND: Pancreatic cancer is a highly malignant digestive tumor. Glutamine metabolism is one of the important sources of tumors. N6-methyladenosine (m6A) modification plays a key role in regulating tumor metabolism and holds promise as a therapeutic target in various cancers, including pancreatic cancer. Disrupting m6A regulation of glutamine metabolism could impair tumor growth, offering potential new therapeutic strategies. However, the functional role of m6A modifications in pancreatic cancer, especially in glutamine metabolism, remains poorly understood. METHODS: The Cancer Genome Atlas (TCGA) dataset and GEPIA bioinformatics tool were used to identify the relationship between m6A related proteins and the glutamine metabolism-associated genes, respectively. The biological effects of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) were investigated using in vitro and in vivo models. Methylated RNA immunoprecipitation sequencing (MeRIP-seq), MeRIP-PCR and RNA immunoprecipitation (RIP) were used to identify solute carrier family 1 member 5 (SLC1A5) as a direct target of IGF2BP2. RESULTS: We found that IGF2BP2 expression and SLC1A5 were significantly correlated and both highly expressed in pancreatic cancer could predict poor prognosis in patients with pancreatic cancer. Functionally, silencing IGF2BP2 suppressed tumor growth and also inhibited glutamine uptake by tumor cells. Mechanistically, IGF2BP2 induced the m6A-SLC1A5-mTORC1 axis, facilitating the upta...