Tumor-derived exosomal microRNA-7-5p enhanced by verbascoside inhibits biological behaviors of glioblastoma in vitro and in vivo.

ABSTRACT

Verbascoside (VB), a glycosylated phenylpropane compound, has been widely used in traditional medicine showing anti-inflammatory and anti-tumor effects in many diseases. The current study aimed to investigate the mechanism underlying the inhibitor effect of VB on glioblastoma (GBM). We isolated and identified the tumor-derived exosomes (TEXs) secreted by GBM cells before and after treatment with VB, after which, we detected expression of microRNA (miR)-7-5p in cells and TEXs by qRT-PCR. Loss- and gain-function assays were conducted to determine the role of miR-7-5p in GBM cells with the proliferation, apoptosis, invasion, migration, and microtubule formation of GBM cells detected. A subcutaneous tumor model and tumor metastasis model of nude mice were established to validate the in vitro findings. We found that VB promoted the expression of miR-7-5p in GBM and transferred miR-7-5p to recipient GBM cells by exosomal delivery. Consequently, miR-7-5p downregulated epidermal growth factor receptor (EGFR) expression to inactivate the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, causing inhibition in the proliferation, migration, invasion, and microtubule formation of GBM cells in vitro, as well as decline in tumor formation and metastasis in vivo. Overall, VB can promote the expression of miR-7-5p in GBM cells and transfer miR-7-5p via exosomes, thereby inhibiting the occurrence of GBM.