Glioma stem cells-derived exosomal miR-26a promotes angiogenesis of microvessel endothelial cells in glioma

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Abstract

Background

Cancer stem cells (CSCs), which are involved in cancer initiation and metastasis, could potentially release exosomes that mediate cellular communication by delivering microRNAs (miRNAs). Based on the role of miR-26a in angiogenesis of glioma, our study was performed to investigate whether glioma stem cells (GSCs)-derived exosomes containing miR-26a could exert effects on angiogenesis of microvessel endothelial cells in glioma, in order to provide a new therapeutic RNA vehicle for glioma therapies.

Methods

The expression of miR-26a and PTEN in glioma was quantified and the interaction among miR-26a, PTEN and PI3K/Akt signaling pathway was examined. Next, a series of gain- and loss-of function experiments were conducted to determine the role of miR-26a in angiogenesis of human brain microvascular endothelial cells (HBMECs). Subsequently, HBMECs were exposed to exosomes derived from GSCs with the gain−/loss-of-function of miR-26a. Finally, the effect of exosomal miR-26a on angiogenesis of HBMECs was assessed both in vitro and in vivo.

Results

The results revealed that PTEN was down-regulated, while miR-26a was up-regulated in glioma. miR-26a activated the PI3K/Akt signaling pathway by targeting PTEN. Restored miR-26a promoted proliferation, migration, tube formation, and angiogenesis of HBMECs in vitro. In addition, GSCs-derived exosomes overexpressing miR-26a contributed to enhanced proliferation and angiogenesis of HBMECs in vitro through inhibition of PTEN. The angiogenic effects of GSCs-derived exosomes overexpressing miR-26a in vivo were consistent with the above-mentioned in vitro findings.

Conclusion

Collectively, our study demonstrates that GSCs-derived exosomal miR-26a promotes angiogenesis of HBMECs, highlighting an angiogenic role of miR-26a via exosomes.

Electronic supplementary material

The online version of this article (10.1186/s13046-019-1181-4) contains supplementary material, which is available to authorized users.

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Most cited references 36

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Author and article information

Contributors

Zhi-Fei Wang: +86-0731-88618218 , wangzhifeidr@163.com

Fan Liao: Drliaofan_LF@163.com

Hao Wu: Drwuhao_WH@163.com

Jin Dai: Drdaijin_DJ@163.com

Journal

Journal ID (nlm-ta): J Exp Clin Cancer Res

Journal ID (iso-abbrev): J. Exp. Clin. Cancer Res

Title: Journal of Experimental & Clinical Cancer Research : CR

Publisher: BioMed Central (London )

ISSN (Print): 0392-9078

ISSN (Electronic): 1756-9966

Publication date (Electronic): 17 May 2019

Publication date PMC-release: 17 May 2019

Publication date Collection: 2019

Volume: 38

Electronic Location Identifier: 201

Affiliations

GRID grid.431010.7, Department of Neurosurgery, , The Third Xiangya Hospital of Central South University, ; No. 138, Tongzipo Road, Changsha, 410013 Hunan Province People’s Republic of China

Article

Publisher ID: 1181

DOI: 10.1186/s13046-019-1181-4

PMC ID: 6525364

PubMed ID: 31101062

SO-VID: 18cb5db1-3861-469a-8253-8f8dd250e03a

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 18 November 2018

Date accepted : 17 April 2019

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: glioma stem cells,exosomes,microrna-26a,microvessel endothelial cells,angiogenesis,phosphatase and tensin homolog deleted on chromosome ten,pi3k/akt signaling pathway

Data availability:

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: glioma stem cells, exosomes, microrna-26a, microvessel endothelial cells, angiogenesis, phosphatase and tensin homolog deleted on chromosome ten, pi3k/akt signaling pathway

Glioma stem cells-derived exosomal miR-26a promotes angiogenesis of microvessel endothelial cells in glioma

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Abstract

Background

Methods

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Conclusion

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Journal of Circulating Biomarkers

Most cited references 36

Exosome secretion: molecular mechanisms and roles in immune responses.

A comprehensive overview of exosomes as drug delivery vehicles - endogenous nanocarriers for targeted cancer therapy.

Alex's Lemonade Stand Foundation Infant and Childhood Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2007-2011.

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