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

Journal of Experimental & Clinical Cancer Research

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