Abstract
FoxR2 plays an important role in the development of many human tumors. However, the effects of FoxR2 on tumorigenicity of human glioma remain unclear. In this study, we investigated the roles of FoxR2 in cell proliferation and invasion of glioma. We found that overexpression of FoxR2 promoted the proliferation, migration and invasion of glioma cells. Knockout of FoxR2 induced G1 arrest by decreasing the expression levels of cyclin D1, cyclin E and p-Rb. Mechanistically, upregulation of FoxR2 increased the level and activity of MMP-2 and decreased the expression of p27. Furthermore, overexpression of FoxR2 decreased the nuclear accumulation of p27. Taken together, these results indicate that upregulation of FoxR2 may confer enhanced tumorigenicity in glioma cells.
Highlights
Malignant gliomas are the most frequent and aggressive central nervous system tumors
Glioma patient samples harbored FoxR2 copy number amplification (4%) and missense mutations (1.8%) by analysis of COSMIC online database. These results indicate that FoxR2 may play a role in the tumorigenicity of glioma
Www.impactjournals.com/oncotarget overexpression of FoxR2 induced a remarkable reduction of nuclear p27 (Figure 6B–6D). These results suggest that FoxR2 may promote glioma cell proliferation, migration and invasion through decreasing the expression and nuclear location of p27
Summary
Malignant gliomas are the most frequent and aggressive central nervous system tumors. Glioblastoma multiforme (GBM) accounts for approximately 60 to 70% of malignant gliomas [1]. There is an urgent need to understand biological signaling mechanisms of cell proliferation and invasion in gliomas. Deregulation of Fox family genes could contribute to glioma proliferation and development [4]. FoxM1 is overexpressed in human GBM and contributes to the tumorigenicity of glioma [5]. The expression of FoxP3 in glioma cells is significantly enhanced after exposure to chemotherapeutics, which induces significant cell apoptosis [7]. These data suggest that the Fox families may serve as potential therapeutic targets for human malignant gliomas
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