Hypoxic Cancer-Secreted Exosomal miR-182-5p Promotes Glioblastoma Angiogenesis by Targeting Kruppel-like Factor 2 and 4

摘要: Glioblastoma (GBM) is the most lethal primary brain tumor and has a complex molecular profile. Hypoxia plays critical role during progression in microenvironment (TME). Exosomes released by cells contain informative nucleic acids, proteins, lipids involved interaction between cancer stromal cells, thus leading to TME remodeling. Accumulating evidence indicates that exosomes play pivotal cell-to-cell communication. However, mechanism which hypoxia affects angiogenesis via derived from remains largely unknown. In our study, we found that, compared with parental under normoxic conditions, GBM produced more exosomes, miR-182-5p was significantly upregulated hypoxic conditions. Exosomal directly suppressed its targets Kruppel-like factor 2 4, accumulation of VEGFR, promoting angiogenesis. Furthermore, exosome-mediated also inhibited tight junction-related proteins (such as ZO-1, occludin, claudin-5), enhancing vascular permeability transendothelial migration. Knockdown reduced proliferation. Interestingly, elevated levels circulating patient blood serum cerebrospinal fluid samples, expression level inversely related prognosis. IMPLICATIONS: Overall, data clarify diagnostic prognostic value tumor-derived reveal distinctive cross-talk human umbilical vein endothelial mediated modulate vasculature.