PolyA RNA seq of human glioblastoma cells treated with a pool of 11 miRNAs in vitro and in vivo (orthotopic tumors in mice)
Glioblastoma (GBM) has a poor prognosis due to infiltrative and therapy-resistant glioma stem-like cells. MicroRNAs (miRNAs) synergistically modulate biological pathways by repressing tumor-related genes, a mechanism lost in cancer. This study aimed to test a combination of different miRNAs exploiting their synergism as a multimodal therapy for GBM. Overall design: In vitro: patient-derived GBM cells (GBM1 and GBM2) were transfected with a pool of 11 miRNAs or with scrambled control, in 2D adherent condition (glioma stem cell medium, matrigel-coated plastic). Cells were then cultured in speroid-permissive condition (glioma stem cell medium, uncoated plastic) for 3 days. In vivo: orthotopic tumors (GBM2 Luc+) were established in NOD/SCID mice striatum; after 42-49 days, animals received intratumoral injection of ApoE-coated LNP loaded with either the 11 miRNA pool or scrambled control. Animals were sacrificed 14 days after treatment and brain dissected to harvest tumoral tissue.