DTL promotes glycolysis and tumor progression in nasopharyngeal carcinoma cells by degrading KAT2B and activating the PI3K/AKT/mTOR pathway

Background Nasopharyngeal carcinoma (NPC) is a prevalent malignancy in East and Southeast Asia, with limited effective treatment options due to late-stage diagnosis. E3 ubiquitin ligase DTL has been implicated in various cancers, but its role in NPC remains obscure. This study aimed to investigate the regulatory mechanisms of DTL in NPC and its potential as a therapeutic target. Methods We conducted a comprehensive analysis combining bioinformatics, immunohistochemistry on clinical specimens, and a series of in vitro and in vivo experiments. Gene expression was analyzed through the GEO database, and the impact of DTL on NPC cell lines was assessed using qRT-PCR, western blotting, and various cellular assays. The interaction between DTL and KAT2B was explored, and the role of the PI3K/AKT/mTOR pathway in DTL-mediated NPC progression was investigated. Results DTL expression was significantly higher in NPC tissues and associated with poor prognosis. DTL knockdown inhibited NPC cell proliferation, migration, and glycolysis, while its overexpression promoted these phenotypes. Mechanistically, DTL interacted with and ubiquitinated KAT2B, leading to its degradation and subsequent activation of the PI3K/AKT/mTOR pathway, which in turn enhanced glycolysis and NPC progression. Conclusions Our findings identify DTL as a critical promoter of NPC, highlighting its potential as a therapeutic target. By targeting the KAT2B-PI3K/AKT/mTOR axis, interventions of DTL could offer a promising strategy for NPC treatment.