Potential Therapeutic Effects of Exosomes Packed With a miR-21-Sponge Construct in a Rat Model of Glioblastoma
Glioblastoma multiforme (GBM) is a 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,...
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doaj-ec8e701cba4d4acda175cc6ea2cc18972020-11-25T01:12:13ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2019-08-01910.3389/fonc.2019.00782443866Potential Therapeutic Effects of Exosomes Packed With a miR-21-Sponge Construct in a Rat Model of GlioblastomaHamideh Monfared0Yavar Jahangard1Maryam Nikkhah2Javad Mirnajafi-Zadeh3Seyed Javad Mowla4Department of Molecular Genetics, Faculty of Biological Science, Tarbiat Modares University, Tehran, IranDepartment of Molecular Genetics, Faculty of Biological Science, Tarbiat Modares University, Tehran, IranDepartment of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, IranDepartment of Physiology, Faculty of Medical Science, Tarbiat Modares University, Tehran, IranDepartment of Molecular Genetics, Faculty of Biological Science, Tarbiat Modares University, Tehran, IranGlioblastoma multiforme (GBM) is a 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.https://www.frontiersin.org/article/10.3389/fonc.2019.00782/fullglioblastomamicroRNAmiR-21exosomessponge |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hamideh Monfared Yavar Jahangard Maryam Nikkhah Javad Mirnajafi-Zadeh Seyed Javad Mowla |
spellingShingle |
Hamideh Monfared Yavar Jahangard Maryam Nikkhah Javad Mirnajafi-Zadeh Seyed Javad Mowla Potential Therapeutic Effects of Exosomes Packed With a miR-21-Sponge Construct in a Rat Model of Glioblastoma Frontiers in Oncology glioblastoma microRNA miR-21 exosomes sponge |
author_facet |
Hamideh Monfared Yavar Jahangard Maryam Nikkhah Javad Mirnajafi-Zadeh Seyed Javad Mowla |
author_sort |
Hamideh Monfared |
title |
Potential Therapeutic Effects of Exosomes Packed With a miR-21-Sponge Construct in a Rat Model of Glioblastoma |
title_short |
Potential Therapeutic Effects of Exosomes Packed With a miR-21-Sponge Construct in a Rat Model of Glioblastoma |
title_full |
Potential Therapeutic Effects of Exosomes Packed With a miR-21-Sponge Construct in a Rat Model of Glioblastoma |
title_fullStr |
Potential Therapeutic Effects of Exosomes Packed With a miR-21-Sponge Construct in a Rat Model of Glioblastoma |
title_full_unstemmed |
Potential Therapeutic Effects of Exosomes Packed With a miR-21-Sponge Construct in a Rat Model of Glioblastoma |
title_sort |
potential therapeutic effects of exosomes packed with a mir-21-sponge construct in a rat model of glioblastoma |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2019-08-01 |
description |
Glioblastoma multiforme (GBM) is a 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. |
topic |
glioblastoma microRNA miR-21 exosomes sponge |
url |
https://www.frontiersin.org/article/10.3389/fonc.2019.00782/full |
work_keys_str_mv |
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