Disruption of DMD gene leads to altered calcium homeostasis and metabolic shift impacting gastric Cancer cell proliferation and migration.

BACKGROUND: DMD gene has been implicated in the progression and development of several tumors, but its specific contribution to gastric cancer (GC) has not been fully elucidated. METHODS: We validated DMD gene expression levels in the TIMER2.0 database and human gastric cancer tissue microarrays and constructed gastric precancerous lesion mouse models and DMD gene knockout and overexpression cell lines to investigate the role of DMD gene in gastric cancer development. RESULTS: In this study, we found that DMD gene is significantly downregulated in GC cells and tissues. Mechanistic analysis revealed that DMD gene deletion increased intracellular calcium levels, disrupted mitochondrial homeostasis, and promoted a metabolic shift towards glycolysis, impacting GC cell proliferation and migration. CONCLUSIONS: Taken together, our results shed light on the novel role of DMD gene in gastric cancer development and provide valuable insights into potential therapeutic strategies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-025-03829-4.