Revealing CASQ1 as a potential target for oral squamous cell carcinoma through gene expression and functional...

Oral squamous cell carcinoma (OSCC) is a significant global health concern, with approximately 377,000 new cases diagnosed annually worldwide. Despite advances in treatment, OSCC remains a leading cause of cancer-related morbidity and mortality, particularly in regions with high prevalence such as Asia and Oceania. In order to identify potential drug targets for OSCC, this study employed an integrative in silico pharmacology strategy. Nineteen GEO transcriptomic datasets (435 samples) were analyzed, 580 significantly overexpressed genes (logFC > 2.5). Network and enrichment analyses highlighted CASQ1 (calsequestrin 1), a calcium-binding protein, as a hub gene within a sarcomeric cluster implicated in epithelial-mesenchymal transition and OSCC progression. To explore its therapeutic potential, molecular docking and 500 ns molecular dynamics (MD) simulations were performed with standard chemotherapeutics, 5-fluorouracil and docetaxel. 5-fluorouracil exhibited strong binding affinity (- 7.225 kcal/mol) and stable conformational dynamics with CASQ1, while docetaxel showed more flexible but persistent binding. These results suggest that CASQ1 is a previously unrecognized drug-interactable target in OSCC and may represent a novel pharmacological vulnerability. Overall, this study demonstrates how integrative computational approaches, spanning gene expression profiling to drug-target interaction modeling, can accelerate target discovery and inform therapeutic strategies in oncology.

The online version contains supplementary material available at 10.1007/s40203-026-00554-2.