Introduction: The mechanism about the glioma remains unclear. Recent studies suggested that glioma would cause the hypoxic microenvironment in the areas of intra- and para-tumor. We hypothesize that glioma has the unique mechanism of aggravating the hypoxic injury of neural cells, which is related with the progression of glioma.
Methods: We observed if there was any hypoxic injury in the para-tumor area through the imaging and pathological examination. Also we carried out the in vitro molecular biological experiments using C6 glioma cell line and normal neuron cells.
Results: In this study we found the definite hypoxic injury of nerve cells in the para-glioma area, which suggested that glioma had the specific mechanism of aggravating the hypoxic injury of the neural cells around the tumor. In indirectly co-culture system, hypoxia would enlarge the ischemic injury of neurons, while the proliferation of C6 glioma cells increased a little bit after hypoxia. Moreover, hypoxia could activate HIF-1a of C6 glioma cells and promote the expression of miRNA-199a-3p in Hypoxia Induced Glioma Derived Exosome (HIGDE) released by C6 cells compared with None Hypoxia Induced Glioma Derived Exosome (NHIGDE). The induced miRNA-199a-3p in HIGDE could aggravate the OGD(Oxygen and Glucose Deprivation) ischemic injury directly in normal cultured neurons in vitro by inhibiting the transcription of mTOR and its down-streams, which suggest HIGDE derived from glioma cells had the definite ability of increase the ischemic injury of the normal neurons.
Conclusions: This study revealed the actual ischemic mechanism in the proliferation and growth of glioma. The in vitro experiments supported that HIGDE and miRNA-199a-3p may exacerbate the hypoxic injury of neurons and facilitate the proliferation of glioma in vivo, which may be an important insight and a potential therapeutic target against brain glioma.
Patient Care: The study supported that HIGDE and miRNA-199a-3p may exacerbate the hypoxic injury of neurons and facilitate the proliferation of glioma in vivo, which may be an important insight and a potential therapeutic target against brain glioma.
Learning Objectives: By the conclusion of this session, participants should be able to: 1)Notice the link between ischemia and tumor growth. 2) Discuss the potential mechanism of hypoxia environment in para-tumor. 3) Identify the effects of HIGDE and miRNA-199a-3p.