SOX15 exerts antitumor function in glioma by inhibiting cell proliferation and invasion via downregulation of Wnt/β-catenin signaling

Aims: Sex-determining region of Y chromosome-related high-mobility-group box 15 (SOX15) has recently emerged as a candidate tumor-inhibitor in multiple types of human tumors. To date, the involvement of SOX15 in glioma is undetermined. The purpose of this study was to investigate the expression, function and potential molecular mechanism of SOX15 in glioma. Main methods: Relative mRNA expression was analyzed by real-time quantitative PCR. Protein expression was determined by Western blot. Cell proliferation was assessed by cell counting kit-8 and colony formation assay. Cell invasion was evaluated by Matrigel invasion assay. Wnt/beta-catenin activation was monitored by luciferase reporter assay. Key findings: SOX15 expression was decreased in glioma tissues and cell lines compared with normal controls. Kaplan-Meier analysis revealed that patients with low expression of SOX15 had shorter survival than those who had high expression of SOX15. The upregulation of SOX15 markedly repressed the proliferation and invasion of glioma cells, whereas its depletion enhanced glioma cell proliferation and invasion. Research into the mechanism revealed that SOX15 exerted an inhibitory effect on Wnt/beta-catenin signaling in glioma cells. Notably, overexpression of beta-catenin partially reversed the SOX15 overexpression-mediated tumor-suppressive effect. In addition, SOX15 overexpression significantly impeded tumor formation by glioma cells in vivo in a mouse xenograft model associated with downregulation of active beta-catenin expression. Significance: These data demonstrate that SOX15 functions as a potential tumor-suppressor in glioma by inhibiting cell proliferation and invasion via the downregulation of Wnt/beta-catenin signaling.