IGF2BP3 binds to FBXO32 to activate the cyclic guanosine monophosphate-protein kinase G pathway, promoting gastric cancer progression

作者：Yi Si, Bo Tian, Rui Zhang, Mingda Xuan, Kunyi Liu, Jiao Jiao, Shuangshuang Han, Hongfei Li, Yanhong Hu, Hongyan Zhao, Wenjing He, Jia Wang, Ting Liu, Weifang Yu · 发表于：World Journal of Gastroenterology · 年份：2025 · DOI：10.3748/wjg.v31.i46.111631 · 被引用次数：3 · 研究领域：Cancer, Hypoxia, and Metabolism、PI3K/AKT/mTOR signaling in cancer、Genomics and Rare Diseases

BACKGROUND N6-methyladenosine (m6A) exerts a pro-carcinogenic effect in diverse cancers. The relationship between m6A-reading protein IGF2BP3 and gastric cancer (GC) has not yet been fully elucidated. AIM To investigate the molecular mechanisms of IGF2BP3 in GC carcinogenesis and progression and thus provide a rationale for novel therapeutic strategies. METHODS Expression levels of IGF2BP3 in GC were determined using quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blot (WB), and immunohistochemistry, and their associations with patients’ clinicopathological characteristics were analyzed. The role of IGF2BP3 in GC was investigated using cellular functional assays and subcutaneous xenograft models, and its downstream targets and signaling pathways were identified using high-throughput sequencing, bioinformatics analysis, RNA immunoprecipitation qPCR, dual luciferase reporter assay, qRT-PCR, and WB. The mechanism of IGF2BP3 in GC was validated via WB and rescue and inhibition experiments. RESULTS IGF2BP3 was highly expressed in GC and associated with diffuse-type GC, incidence of lymph node metastasis, advanced tumor node metastasis stage, and deeper tumor invasion depth. In vitro experiments demonstrated that IGF2BP3 promoted proliferation, migration, and invasiveness of GC cells, while inhibiting apoptosis and augmenting intracellular levels of glucose metabolism. In vivo experiments revealed that IGF2BP3 contributes to the growth of GC. Mechani...