MicroRNA and gap junctions in glioblastoma cells: Implications for cellular therapy

Abstract

Glioblastoma (GBM), the most common and aggressive adult human primary brain tumor, has poor prognosis with the median survival of 11 months. Several major cellular pathways linked to cell growth and survival, have been characterized in GBM. The frontline therapy for GBM, Temozolomide (TMZ), induces its own resistance, partly through miRNA-9. The increase in miRNA-9 decreases the translation of Patch receptor, resulting in enhanced hedgehog signaling and induced expression of the multiple drug resistance gene. CD133+ GBM cells, which have been thought to be the early cell type, expressed high levels of miRNA-9, indicating that this miR can be a target. The TMZ-resistant GBM cells can transfer miRNA-9 among cells through gap junctions and through the release of small vesicles, in particular exosomes. Here we discussed how these findings can be applied to develop new treatments for a disease with poor prognosis.