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

• Published in: Journal of experimental & clinical cancer research 2019-05, Vol.38 (1), p.201-201, Article 201
• Main Authors: Wang, Zhi-Fei, Liao, Fan, Wu, Hao, Dai, Jin
• Format: Article
• Language: English
• Subjects: Adult; Aged; Angiogenesis; Animals; Biomarkers; Brain; Brain cancer; Brain research; Cancer; Cancer metastasis; Cancer therapies; Care and treatment; Cell growth; Cell Movement - genetics; Cell Proliferation - genetics; Cellular signal transduction; Coculture Techniques; Endothelial Cells - metabolism; Endothelial Cells - pathology; Endothelium; Exosomes; Exosomes - genetics; Exosomes - pathology; Female; Gene expression; Gene Expression Regulation, Neoplastic - genetics; Genetic aspects; Glioma; Glioma - genetics; Glioma - pathology; Glioma stem cells; Gliomas; Heterografts; Humans; Laboratory animals; Male; Medical prognosis; Mice; MicroRNA; microRNA-26a; MicroRNAs - genetics; Microvessel endothelial cells; Microvessels - metabolism; Microvessels - pathology; Middle Aged; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Neovascularization; Phosphatase and tensin homolog deleted on chromosome ten; Phosphatases; Phosphatidylinositol 3-Kinases - genetics; Prognosis; Prostate cancer; Proto-Oncogene Proteins c-akt - genetics; PTEN Phosphohydrolase - genetics; Risk factors; RNA; Signal Transduction - genetics; Stem cell transplantation; Stem cells; Tumors
• ISSN: 1756-9966; 0392-9078; 1756-9966
• DOI: 10.1186/s13046-019-1181-4

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