Using 6 highly invasive glioblastoma (GBM) PDOX models, this study isolates matching pairs of invasive (GBMINV) and tumor core (GBMTC) cells, demonstrates an elevated invasion capacity in GBMINV cells, identifies a novel miRNA signature (miRNAINV) of GBM invasion, and discovers a commonly shared gene, KCNA1, from miRNAINV regulated genes that can be pharmacologically inhibited to block GBM invasion in vivo. This evidence concerns the gene KCNA1 and glioblastoma.