Dihydroartemisinin Suppressed Cell Migration and Promoted Autophagy through RALB in Tongue Squamous Cell Carcinoma

Background: Overexpression of RAS-like proto-oncogene B (RALB), a member of the RAS-like Guanosine triphosphatase (GTPase) family, is significantly associated with poorer overall survival in patients with head and neck squamous cell carcinoma (HNSCC). However, potential drugs that inhibit RALB remain unknown. Methods: Differentially expressed genes (DEGs) in HNSCC were identified using the The Cancer Genome Atlas - Head and Neck Squamous Cell Carcinoma (TCGA-HNSC) dataset. Genes associated with the Rat sarcoma virus (RAS) signaling pathway were retrieved from the GeneCards database, the National Center for Biotechnology Information (NCBI) Gene resource, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database. Subsequently, experimental validation was conducted using Cal-27 human tongue squamous cell carcinoma cells. First, wound-healing and colony-formation assays were performed, followed by treatment with dihydroartemisinin (DHA). Finally, an orthotopic xenograft model was established by implanting shRALB-Cal-27 cells into the tongues of BALB/c nude mice, which were then treated with DHA. Results: We found that RALB expression was correlated with N stage and closely related to patient survival in HNSCC. RALB knockdown promoted autophagyin Cal-27 cells. Moreover, DHA significantly inhibited the proliferation and migration in Cal-27 cells. DHA increased the expression levels of P62 and LC3B in the tongues of nude mice implanted with shRALB-Cal-27 cells. Conclusion: DHA inhibited migration and promoted autophagy through RALB in tongue squamous cell carcinoma (TSCC).