Monfared Hamideh, Jahangard Yavar, Nikkhah Maryam, Mirnajafi-Zadeh Javad, Mowla Seyed Javad
Department of Molecular Genetics, Faculty of Biological Science, Tarbiat Modares University, Tehran, Iran.
Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
Front Oncol. 2019 Aug 20;9:782. doi: 10.3389/fonc.2019.00782. eCollection 2019.
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, and . 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.
多形性胶质母细胞瘤（GBM）是4级胶质瘤，也是最具侵袭性的胶质瘤形式，对当前治疗反应不佳。微小RNA（miRNA）的表达在包括GBM在内的各种癌症中广泛失调。GBM中过表达的miRNA之一是miR-21，它促进肿瘤细胞的增殖、侵袭和转移行为。细胞外囊泡“外泌体”大小为30-100纳米，已成为一种新型且强大的药物递送系统。最近，miRNA或抗miRNA向肿瘤细胞的外泌体转移为miRNA对抗癌症的治疗应用引入了一种新方法。在此，我们试图通过使用装载有miR-21海绵构建体的工程化外泌体来下调胶质瘤细胞系U87-MG和C6中的miR-21表达。我们的数据显示，工程化外泌体有潜力抑制miR-21，从而上调miR-21的靶基因。有趣的是，在用miR-21海绵外泌体处理的细胞中，我们观察到增殖下降，凋亡率升高。最后，在胶质母细胞瘤大鼠模型中，给予装载有miR-21海绵构建体的外泌体导致肿瘤体积显著减小。简而言之，我们的研究结果提出了一种新的治疗策略，即使用工程化外泌体将miR-21海绵构建体递送至GBM细胞，以阻断其恶性行为。
