Journal of Experimental & Clinical Cancer Research | |
Glioma stem cells-derived exosomal miR-26a promotes angiogenesis of microvessel endothelial cells in glioma | |
Hao Wu1  Fan Liao1  Jin Dai1  Zhi-Fei Wang1  | |
[1] grid.431010.7, Department of Neurosurgery, The Third Xiangya Hospital of Central South University, No. 138, Tongzipo Road, 410013, Changsha, Hunan Province, People’s Republic of China; | |
关键词: Glioma stem cells; Exosomes; microRNA-26a; Microvessel endothelial cells; Angiogenesis; Phosphatase and tensin homolog deleted on chromosome ten; PI3K/Akt signaling pathway; | |
DOI : 10.1186/s13046-019-1181-4 | |
来源: publisher | |
【 摘 要 】
BackgroundCancer 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.MethodsThe 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.ResultsThe 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.ConclusionCollectively, our study demonstrates that GSCs-derived exosomal miR-26a promotes angiogenesis of HBMECs, highlighting an angiogenic role of miR-26a via exosomes.
【 授权许可】
CC BY
【 预 览 】
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