Study of MiR-451 in the Treatment of Human Gliomas through Regulating the AMPK Pathway Mediated by Bone Mesenchymal Stem Cells

Abstract

\n Accumulating evidence has suggested that gene therapy plays critical roles in glioma treatment. Our previous studies demonstrated that miR-451 could be used as a tumor suppressor via targeting CAB39. But the ability for the targeted delivery of miR-451 to glioma was a significant issue. Bone marrow mesenchymal stem cells (BMSCs) have been used for systemic delivery of therapeutic genes to solid tumors. In the present study, hBMSCs were used as gene therapy non-viral vectors of miR-451 to treat glioma cells in vitro and in vivo. First, following the treatment of glioma cells with the culture medium of miR-451-loaded hBMSCs via lentivirus, overexpression of miR-451 in glioma cells suppressed its proliferation, migration and invasion, but enhanced cell apoptosis by targeting CAB39 and the LKB1/AMPK/HIF-1α/VEGF pathways. Secondly, Transwell migration assays further demonstrated the chemotaxis of BMSCs to glioma conditioned media in vitro. Lastly, it was verified that the miR-451-loaded hBMSCs could effectively deliver miR-451 to the tumor region and prolong the survival in xenograft model assays. These results indicated that gene therapy using hBMSCs as vehicles was highly effective in a mice glioma model and therefore hold considerable prospects of clinical transformation.