Neural stem cell-derived exosomes transfer miR-124-3p into cells to inhibit glioma growth by targeting FLOT2

Abstract

Currently, exosomes (EXOs) are being explored as novel drug delivery carriers with greater advantages, including crossing the blood-brain-barrier and loading drugs. The present study utilized EXOs derived from neural stem cells (NSCs) for the delivery of molecular drugs to treat gliomas. miR-124-3p was selected according to previous studies by the authors, and the effects of the delivery of miR-124-3p to glioma cells by NSC-EXOs in vitro and in vivo were evaluated. It was found that NSC-EXOs successfully delivered miR-124-3p into glioma cells, and NSC-EXOs loaded with miR-124-3p significantly inhibited glioma cell proliferation, invasion and migration. Furthermore, the delivery of miR-124-3p by NSC-EXOs suppressed flotillin 2 (FLOT2) expression by specifically binding to the 3' untranslated region of the FLOT2 gene in gliomas; subsequently, AKT1 was found to be associated with the EXO-miR-124-3p/FLOT2 pathway. Moreover, the therapeutic effects of the delivery of miR-124-3p by NSC-EXOs were confirmed in a mouse tumor xenograft model of glioma. Thus, bio-carrier NSC-EXOs loaded with miR-124-3p suppressed glioma growth via the EXO-miR-124-3p/FLOT2/AKT1 pathway. On the whole, the present study provides insight into stem cell-free molecular-targeted therapy based on bio-carrier NSC-EXOs and provides a potential strategy for the treatment of glioma.