Introduction: Forkhead box (FOX) superfamily members were recently shown to play important roles in tumor development and progression. Forkhead box S1 (FOXS1), a member of the FOX family, has been reported to be closely associated with malignant neoplasms. However, its expression and effect on hepatocellular carcinoma remain unclear. The aim of this study was to determine the expression and role of FOXS1 in hepatocellular carcinoma (HCC).
Methods: Real-time PCR, Western blot and immunohistochemistry assays were carried out to determine FOXS1 expression in HCC tissues and cells. The biological roles of FOXS1 in HCC were investigated using CCK-8, colony formation, transwell and wound healing. Additionally, the effect of FOXS1 on epithelial–mesenchymal transition (EMT) was investigated by Western blotting. Xenograft model was carried out to evaluate the effect of FOXS1 in vivo.
Results: In our study, we confirmed lower FOXS1 expression in HCC samples than in normal liver tissues by performing Western blotting, immunohistochemistry and real-time PCR assays. In addition, FOXS1 expression is strongly associated with the prognosis of patients with HCC. Overexpression of FOXS1 suppressed cell proliferation, colony formation, the epithelial–mesenchymal transition (EMT) and the hedgehog (Hh) signaling pathway in vitro and in vivo. SAG, an activator of Hh signaling, partially reversed the effect of FOXS1 overexpression on HCC cells.
Conclusion: FOXS1 might suppress HCC cell proliferation, colony formation, and EMT by inhibiting the Hh signaling pathway, indicating that FOXS1 may be a promising biological target in HCC.
Keywords: FOXS1, epithelial–mesenchymal transition, hepatocellular carcinoma, hedgehog pathway