title: Up-regulation of microRNA-16 in Glioblastoma Inhibits the Function of Endothelial Cells and Tumor Angiogenesis by Targeting Bmi-1.
abstract: BACKGROUND
  Angiogenesis is an important process facilitating the growth of glioblastoma (GBM). It also has drawn great attention in the treatment of GBM. GBM angiogenesis is closely related to the function of endothelial cells. microRNAs can affect the activities of endothelial 10 cells directly, or indirectly through the interaction of tumor cells and endothelial cells. However, the mechanism underlying the interaction of GBM cells regulated by specific microRNA with endothelial cells and following angiogenesis requires further research. In published articles, microRNA-16 acted as a tumor suppressor in multiple types of cancers including glioma, but the role in glioma angiogenesis has not been well elucidated.
  
  
  METHODS
  The expression of microRNA-16 was detected in human GBM samples and normal brain tissues. microRNA-16 was transfected to GBM cell line U87 and A172 then the function of endothelial cells co-cultured with U87/A172 (miR-16 or control) were observed in vitro. Expression of VEGF family in vitro and the effect of microRNA-16 on GBM angiogenesis in vivo were also investigated.
  
  
  RESULTS
  microRNA-16 is down-regulated in human GBM samples in contrast to the normal brain tissues. Overexpression of microRNA- 16 in the A172 and U87 GBM cell lines inhibited the activities of co-cultured endothelial cells, including proliferation, migration, extension and tubule formation. Further experiments of dual luciferase assays verified microRNA-16 directly targeting Bmi-1. microRNA-16 down-regulated the expression of vascular endothelial growth factor VEGF-A and VEGF- C which were closely related to the angiogenesis of GBM. Moreover, less vascular formed in the section of neoplasm of the microRNA- transduced group than the control group in vivo.
  
  
  CONCLUSIONS
  Collectively, these findings indicate that loss of microRNA-16 may favor glioma angiogenesis, on the contrary overexpression of microRNA-16 in GBM cells plays a critical role in repressing endothelial function and angiogenesis by targeting Bmi-1. microRNA-16 may be a potential therapeutic agent in the treatment of GBM.
authors.forename: Fanfan
authors.initials: F
authors.lastname: Chen
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Hua
authors.initials: H
authors.lastname: He
authors.forename: Weiyi
authors.initials: W
authors.lastname: Huang
authors.forename: Run
authors.initials: R
authors.lastname: Zhang
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Meng
authors.affiliation: The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China. jiangxiao_dan@163.com.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Jiang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D005909:Glioblastoma / Q000098:blood supply* / Q000235:genetics*; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000378:metabolism; D063150:Polycomb Repressive Complex 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: C069077:BMI1 protein, human; C505362:MIRN16 microRNA, human; D035683:MicroRNAs; D063150:Polycomb Repressive Complex 1