Research on the Mechanism of Cuproptosis-related Gene LIAS in Regulating Nasopharyngeal Carcinoma

Abstract Background Nasopharyngeal carcinoma (NPC) is a malignant tumor with a high incidence in endemic regions, and the identification of novel therapeutic targets remains essential. Lipoic acid synthetase (LIAS), a key regulator of mitochondrial metabolism and a cuproptosis-related gene, has been implicated in tumor progression; however, its role in NPC remains unclear. Results LIAS expression was evaluated in NPC tissues and cell lines, and its effects on proliferation, migration, invasion, energy metabolism, and Elesclomol-CuCl₂ (ES-Cu)-induced cuproptosis were assessed in vitro. Transcriptomic sequencing, co-immunoprecipitation (Co-IP), and molecular simulations were used to explore the mechanism, with in vivo validation in a xenograft model. LIAS was downregulated in NPC tissues and cell lines. LIAS overexpression suppressed malignant behaviors, altered energy metabolism, and increased sensitivity to ES-Cu-induced cuproptosis. Transcriptomic analysis identified LHPP as a downstream target. LIAS positively regulated LHPP expression and interacted with LHPP. LHPP overexpression enhanced the inhibitory effects of LIAS, whereas the LHPP R157A mutation partially attenuated these effects. In vivo , LIAS overexpression combined with ES-Cu further inhibited tumor growth and enhanced cuproptosis-related changes. Conclusion LIAS suppresses NPC progression and enhances sensitivity to ES-Cu induced cuproptosis, potentially through regulation of the LIAS-LHPP axis and cellular energy metabolism. These findings provide new insights into the molecular mechanisms of NPC and the potential application of cuproptosis based therapeutic strategies.