Hypoxia-Induced Glioma-Derived Exosomal miRNA-199a-3p Promotes Ischemic Injury of Peritumoral Neurons by Inhibiting the mTOR Pathway

Figure 8

A schematic summarization of the key findings. HIGDE miRNA-199a-3p can be upregulated by hypoxia-induced HIF-1α activation and then is able to increase ischemic injury of peritumoral neurons by inhibiting the mTOR pathway. The region we focused on in the current study was the red triangle in (a) and (b). (a) Blue region: glioma lesion; yellow region around the lesion: hypoxia region. (b) The glioma lesion and its surrounding hypoxic region in MRI T1 enhanced scanning. (c, d) The microenvironment of the peritumoral region. Blue background: intratumoral hypoxia region. Dark yellow background: peritumoral hypoxia region. Light yellow background: normal brain nonhypoxic region. As the hypoxic condition worsened, HIF-1α was activated and increased the level of miRNA-199a-3p in the exosomes secreted by glioma cells (light blue ball: NHIGDE; dark blue ball: HIGDE). Then, exosomes were released and inhibited the mTOR level in peritumoral normal neurons. Thus, hypoxia-induced injuries of peritumoral neurons were aggravated, and glioma growth was also facilitated.