Transcription factor c-jun regulates 3Gn-T8 expression in gastric cancer cell line SGC-7901

摘要

Aberrant glycosylation, a common feature of malignant alteration, is partly due to changes in the expression of glycosyltransferases, including 1,3-N-acetyl-glucosaminyltrans ferase 8 (3Gn-T8), which synthesizes poly-N-acetyllactosamine (poly-LacNAc) chains on 1,6 branched N-glycans. Although the role of 3Gn-T8 in tumors has been reported, the regulation of 3Gn-T8 expression, however, is still poorly understood. In the present study, we used three online bioinformatic software tools to identify multiple c-jun binding sites in the promoter of the 3Gn-T8 gene. Using luciferase reporter assay, chromatin immunoprecipitation (ChIP) analysis, RT-PCR and western blot analysis, we revealed that c-jun could bind to and activate the 3Gn-T8 promoter, thus upregulating 3Gn-T8 expression. This was also confirmed by changes in 3Gn-T8 activity as demonstrated by flow cytometry, immunofluorescence and lectin blot analysis using LEA lectin. Moreover, expression of glycoprotein HG-CD147, the substrate of 3Gn-T8, was also regulated by c-jun. In addition, c-jun and 3Gn-T8 were more highly expressed in the gastric cancer tissues when compared to these levels in the adjacent non-tumor gastric tissues, and 3Gn-T8 expression was positively correlated with c-jun expression. These results suggest that c-jun plays a significant role in regulating the expression of 3Gn-T8 in the SGC-7901 cell line and may be involved in the development of malignancy via the activity of 3Gn-T8.