LG-23: MicroRNA519d AND microRNA4758 IN DISTINGUISHING GANGLIOGLIOMA FROM DYSEMBRYOPLASTIC NEUROEPITHELIAL TUMORS AND ASTROCYTOMAS

Glioneuronal tumors, including gangliogliomas (GG) and dysembryoplastic neuroepithelial tumors (DNT), represent the most common long-term epilepsy associated tumors (LEAT) and are a well-recognized cause of chronic intractable focal epilepsy in children and young adults. MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression involved in the pathogenesis of different neurological diseases and in oncogenesis. The present study investigated the differential expression of miR519d and miR4758 in GG compared to DNT and astrocytomas and studied their functional implications. MiRNA expression was screened in control cortex (n = 5) and GG (n = 6) using the miRCURY LNA™ miRNA array. Subsequently, the expression of miR519d and miR4758 and their predicted gene targets was validated using qPCR in GG (n = 16), DNT (n = 12) and astrocytomas (n = 39, grade II-IV). The effect of overexpression or knockdown of miR519d and miR4758 on their targets, using miRNA mimics and inhibitors respectively, was studied in a low grade astrocytoma cell line (Res-259). Additionally, their effect on cell proliferation was measured using the propidium iodide cell cycle assay. Both miR519d and miR4758 were significantly upregulated in GG but not DNT or astrocytomas as compared to control cortex. Furthermore, AKT3, a predicted gene target of miR519d and miR4758, was downregulated in GG. Functionally, overexpression of miR519d in an astrocytic cell line resulted in a downregulation of AKT3 and an increase in cell proliferation whereas co-transfection with miR4758 counteracted this effect. The results suggest that miR519d may act as a regulator of cell cycle in low grade gliomas and may serve as a biomarker for GG.