SOX1 promotes osteosarcoma metastasis by modulating TSPAN12 expression

Background: Osteosarcoma is the most common primary bone malignancy, with a strong tendency towards local invasion and metastasis. The SRY-Box Transcription Factor 1 (SOX1) gene, a member of the HMG-box family of DNA-binding transcription factors, plays a crucial role in embryogenesis and tumorigenesis. However, its role in osteosarcoma, particularly in relation to metastatic potential, is not well understood. Methods: The GSE14359 dataset containing five samples of conventional osteosarcoma and four samples of lung metastatic osteosarcoma was obtained from the Gene Expression Omnibus (GEO) database and analyzed for differential gene expression using the R language. Gene expression was detected using qPCR and Western blotting. Transcriptional activity was assessed by Luciferase reporter gene assays, and cell metastatic ability was assessed by migration and invasion assays. Results: The study demonstrated that SOX1 binds to a specific response element within the Transmembrane 4 Superfamily Member 12 (TSPAN12) promoter, upregulating TSPAN12 and its associated inflammatory pathways. Silencing TSPAN12 markedly reduces SOX1-mediated osteosarcoma cell invasion and inflammatory response, while TSPAN12 overexpression reverses these effects in SOX1-suppressed cells. Conclusion: In this study, our findings elucidate SOX1's role in enhancing osteosarcoma metastasis via TSPAN12 upregulation, offering new insights into the molecular mechanisms of osteosarcoma progression.