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
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.