Downregulation of sialyl-transferases and their role in malignant meningioma cells.

Meningiomas are the most common primary intracranial tumors and are often curable with gross resection. However, surgery is not entirely effective, as recurrences are reported more frequently in patients with meningiomas with higher-grade tumors, despite the extent of surgical resection. Therefore, elucidating tumor biology at the molecular level is needed. Aberrant sialylation, resulting from altered expression of sialyl-transferases (STs), plays an important role in cancer development and progression. However, the role of altered sialylation in meningioma progression remains unclear. In the present study, downregulation of β-galactoside α2,3-ST (ST3Gals) and β-galactoside α2,6-ST (ST6Gals) genes was found in malignant meningioma tissues from four different Gene Expression Omnibus (GEO) datasets (GEO entries: GSE16581, GSE43290, GSE74385 and GSE136661). Moreover, suppression of sialylation using a pan-sialylation inhibitor (3Fax-peracetyl-Neu5Ac, 3Fax) reduced the activity of STs in a malignant meningioma cell line, leading to an increase in cell migration and invasion capacities. Further investigation of epithelial-mesenchymal transition (EMT) markers, AKT, and ERK signaling in the 3Fax-treated cell lines revealed that high expression of EMT-related transcription factors (Snail) and EMT-related proteins (MMP9) were regulated via phosphorylation of AKT and ERK. Therefore, the present findings suggested that suppression of sialylation by 3Fax in malignant meningioma increases migration and invasion abilities by enhancing the EMT process.