FOXO3 and central nervous system cancer: As shown in Figure 5B, overexpression of SPHK1 indeed significantly reduced the activity of luciferase in the glioma cells, whereas the transcriptional activity of FOXO3a was elevated significantly in SPHK1 downregulated glioma cells, further suggesting that SPHK1 expression attenuated gene transcription driven by FOXO3a in glioma cells.