Integrated multi-omics and functional analysis uncovers the structural and regulatory significance of Nucleophosmin 1 in the metabolic progression of esophageal carcinoma

Esophageal carcinoma (ESCA) is characterized by high mortality and metabolic reprogramming. This study investigated the expression, functional role, and regulatory mechanisms of Nucleophosmin 1 (NPM1) in ESCA, specifically examining its link to glycolysis and competing endogenous RNA (ceRNA) networks. Integrated bioinformatics analysis of TCGA and GEO datasets, validated by immunohistochemistry, revealed that NPM1 is significantly overexpressed in ESCA tissues and correlates with clinical stage. In vitro loss-of-function assays demonstrated that NPM1 silencing suppresses cell proliferation, migration, and viability while altering cell cycle distribution and Apoptosis. Crucially, Gene Set Enrichment Analysis (GSEA) and functional experiments-including 2-NBDG uptake assays-established a positive correlation between NPM1 and glycolytic activity, confirming that NPM1 knockdown impairs glycolysis. Furthermore, a potential MIR4435-2HG/hsa-miR-125a-5p/NPM1 ceRNA axis was identified. Collectively, these findings indicate that NPM1 contributes to ESCA progression via metabolic modulation and ceRNA regulation, supporting its utility as a prognostic biomarker and therapeutic target.

Diagnostic markers; Esophageal carcinoma; Glycolysis; NPM1; ceRNA.