Tumor-derived exosomal microRNA-7-5p enhanced by verbascoside inhibits biological behaviors of glioblastoma in vitro and in vivo
Author(s) -
Huan Wang,
Jiugeng Feng,
Ao Fan,
Yiqiang Tang,
Pengliang Xu,
Min Wang,
Min Huang
Publication year - 2020
Publication title -
molecular therapy — oncolytics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.424
H-Index - 23
ISSN - 2372-7705
DOI - 10.1016/j.omto.2020.12.006
Subject(s) - microvesicles , cancer research , protein kinase b , in vivo , pi3k/akt/mtor pathway , microrna , metastasis , verbascoside , epidermal growth factor receptor , in vitro , apoptosis , chemistry , biology , signal transduction , medicine , microbiology and biotechnology , receptor , cancer , biochemistry , glycoside , organic chemistry , gene
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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