Conversely, miRNA181a-5p can regulate either total STAT3 levels in U87 cells and, notably, affect levels of p-STAT3 in the primary GBM cell line GBM42, indicating an unknown mechanism of kinase regulation by miRNA, similar to an observation made for phospho-AKT and p-ERK in a previous study in glioma (42) Previously, the importance of STAT3 signaling in GBM has been demonstrated in numerous studies whilst our group showed that ADAM8 dependent activation of STAT3 signaling led to increased angiogenesis by upregulation of osteopontin (10, 43, 44, reviewed in 45). This evidence concerns the gene SPP1 and glioma.