Cordycepin-mediated transcriptional regulation of human GD3 synthase （hST8Sia 1） in human neuroblastoma SK-N-BE（2）-C cells

In the present study, we firstly found that cordycepin ele- vated the gene expression of the human GD3 synthase （hST8Sia 1） in human neuroblastoma SK-N-BE（2）-C cells. To elucidate the mechanism underlying the upregulation of hST8Sia I gene expression in cordycepin-treated SK-N- BE（2）-C cells, functional characterization of the promoter region of the hST8Sia 1 gene was performed. Analysis of promoter activity using varying lengths of 5r-flanking region showed a dramatic increase by cordycepin in the -1146 to --646 region, which contains putative binding sites for transcription factors c-Ets-1, CREB, AP-1, and NF-κB. Site- directed mutagenesis for these binding sites and chromatin immunoprecipitation assay revealed that the NF-κB binding site at - 731 to - 722 is essential for the cordycepin-induced expression of the hST8Sia I in SK-N-BE（2）-C cells. Moreover, the hST8Sia I expression induced by cordycepin was significantly repressed by pyrrolidinedithiocarbamate, an inhibitor of NF-KB. These results suggested that cordycepin induces upregulation of hST8Sia I gene expression through NF-κB activation in SK-N-BE（2）-C cells.