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The IGF1-PGM5 Axis Inhibits Aerobic Glycolysis and Serves As a Tumor Suppressor in Nasopharyngeal Carcinoma
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DOI：10.1002/jbt.70988.png)
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Abstract
En 中文
Nasopharyngeal carcinoma (NPC) is a prevalent malignancy with a distinct geographical distribution. This study aimed to identify core glycolysis-related genes and investigate their functional roles in NPC pathogenesis. Integrated transcriptomic analysis was performed on multiple Gene Expression Omnibus datasets. Screening of core genes was performed computationally via machine learning algorithms on the pool of glycolysis-related differentially expressed genes (Gly-DEGs). The tumor-suppressive function of insulin-like growth factor 1 (IGF1) was demonstrated through a combination of in vitro assays, assessing proliferation, migration, invasion, apoptosis, and glycolysis, followed by validation in xenograft models. Co-immunoprecipitation (Co-IP) examined IGF1-PGM5 interaction; Western blotting measured IGF1R and p-IGF1R levels. PGM5 involvement was tested by knockdown rescue. IGF1 was identified as a significantly downregulated core gene in NPC. Its overexpression inhibited NPC cell proliferation, migration, invasion, and promoted apoptosis, while simultaneously suppressing glycolysis, evidenced by reduced glucose consumption, lactate production, and expression of key glycolytic enzymes hexokinase 2 (HK2) and lactate dehydrogenase A (LDHA). These findings were corroborated in vivo. Co-IP revealed a direct physical interaction between IGF1 and PGM5. IGF1 overexpression did not alter total IGF1R or p-IGF1R levels, indicating IGF1R-independent action. IGF1 positively correlated with PGM5, and PGM5 knockdown attenuated IGF1's tumor-suppressive and glycolytic-inhibitory effects. In NPC, IGF1 serves to suppress tumor progression, inhibiting malignant phenotypes and aerobic glycolysis through the upregulation of PGM5. The IGF1-PGM5 axis represents a novel metabolic regulatory pathway that may warrant further investigation as a potential therapeutic target for NPC intervention.
Keywords:
Aerobic glycolysis
IGF1
Nasopharyngeal carcinoma
PGM5
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