HPRT1 activates glycolysis to promote proliferation and metastasis of lung adenocarcinoma

Objective: This study investigated whether hypoxanthine phosphoribosyltransferase 1 (HPRT1) regulates malignant biological behavior in lung adenocarcinoma (LUAD) through glycolysis. Methods: Glycolysis-related genes associated with LUAD prognosis were screened by bioinformatics analyses. HPRT1 expression was examined in LUAD cell lines and normal bronchial epithelial cells. HPRT1 knockdown and overexpression models were established in H1299 and A549 cells, respectively. Cell proliferation, migration and invasion were assessed using CCK-8, colony formation, wound-healing and Transwell assays. Glycolytic activity was evaluated by lactate measurement and Western blotting of hexokinase 2 (HK2) and pyruvate kinase M2 (PKM2), with 2-deoxy-D-glucose (2-DG) used for rescue experiments. Results: HPRT1 was identified as a glycolysis-related gene with prognostic relevance in LUAD. HPRT1 was highly expressed in H1299 cells and weakly expressed in A549 cells. HPRT1 knockdown inhibited proliferation, migration and invasion, whereas HPRT1 overexpression promoted these malignant phenotypes. HPRT1 also increased lactate production and upregulated HK2 and PKM2. Treatment with 2-DG suppressed glycolysis and reversed the HPRT1-induced enhancement of proliferation, migration and invasion. Conclusion: HPRT1 promotes malignant biological behavior in LUAD cells by activating glycolysis, suggesting that HPRT1 may be a potential metabolic therapeutic target.