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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.00782

Potential therapeutic effects of exosomes packed with a miR-21-sponge construct in a rat model of glioblastoma

  • 1Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Iran
  • 2Tarbiat Modares University, Iran

Glioblastoma multiforme (GBM) is the grade 4 and the most aggressive form of glioma, with a poor response to current treatments. The expression of microRNAs (miRNAs) is widely dysregulated in various cancers, including GBM. One of the overexpressed miRNAs in GBM is miR-21 which promotes proliferation, invasion and metastatic behaviors of tumor cells. With a size of 30-100 nm, the extracellular vesicles “exosomes” have emerged as a novel and powerful drug delivering systems. Recently, exosomal transfer of miRNAs or anti-miRNAs to tumor cells has introduced a new approach for therapeutic application of miRNAs to combat cancer. Here, we have tried to down-regulate miR-21 expression in glioma cell lines, U87-MG and C6, by using engineered exosomes, packed with a miR-21-sponge construct. Our data revealed that the engineered exosomes have the potential to suppress miR-21 and consequently to upregulate miR-21 target genes, PDCD4 and RECK. Interestingly, in cells treated with miR-21-sponge exosomes we observed a decline in proliferation and also an elevation in apoptotic rates. Finally, in a rat model of glioblastoma, administrating exosomes loaded with a miR-21-sponge construct leads to a significant reduction in the volume of the tumors. In brief, our findings suggest a new therapeutic strategy to use engineered exosomes to deliver a miR-21-sponge construct to GBM cells, in order to block its malignant behavior.

Keywords: Glioblastoma, microRNA, miR-21, sponge, exosome

Received: 28 Mar 2019; Accepted: 01 Aug 2019.

Edited by:

Thomas Daubon, Institut National de la Santé et de la Recherche Médicale (INSERM), France

Reviewed by:

Ioannis S. Pateras, National and Kapodistrian University of Athens, Greece
Jun Wei, University of Texas MD Anderson Cancer Center, United States  

Copyright: © 2019 Monfared, Jahangard, Nikkhah, Mirnajafi-Zadeh and Mowla. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Seyed Javad Mowla, Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Alborz, Iran, sjmowla@modares.ac.ir