Tumor-derived exosomal microRNA-7-5p enhanced by verbascoside inhibits biological behaviors of glioblastoma in vitro and in vivo
Huan Wang, Jiugeng Feng, Fan Ao, Yiqiang Tang, Pengliang Xu, Min Wang, Min Huang
Journal:Molecular Therapy-Oncolytics
IF:4.12
DOI:10.1016/j.omto.2020.12.006
PMID:33768139
Published:2020-12-19
research field:肿瘤学分子生物学药理学
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.
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