From: Cancer stem cell contribution to glioblastoma invasiveness
microRNA | Biological function | Reference |
---|---|---|
miR-7 | Downregulated in GBM. Acts as a tumor suppressor in GBM, preventing GBM CSC invasion, proliferation, and survival by repressing EGFR and its downstream pathway AKT on one side and FAK and the production of MMP-2 and MMP-9 on the other side. | |
miR-10b | Acts as oncogene: it is overexpressed in glioma samples. Induces glioma cell invasion in vitro by decreasing HOXD10 protein levels, which in turn control MMP-14 and uPAR expression, resulting in their upregulation. | [101] |
miR-21 | Acts as oncogene: it is overexpressed in GBM, where it represses the MMP inhibitors TIMP3 and RECK, thus resulting in metalloproteinase MMP-2 upregulation, promoting glioma invasion and angiogenesis. High levels of this miR are associated with poor patient survival. | |
miR-23b | Acts as a tumor suppressor and is downregulated at the invasive edge in GBM. Pyk2, whose expression is higher in high-grade gliomas, is one of its direct targets. | [110] |
miR-34a | Acts as a tumor suppressor and is downregulated in human glioma tumors as compared with normal brain. Its overexpression exerts a suppressive effect in GBM CSCs by inhibiting proliferation and migration while inducing differentiation (Guessous et al. [111]). | [111] |
miR-101 | Acts as a tumor suppressor and is downregulated in GBM. Its target EZH2, a histone metyl transferase belonging to the Polycomb Group of proteins, is therefore overexpressed, promoting cell migration, neo-angiogenesis, and cell growth. | [112] |
miR-124a | Acts as a tumor suppressor and is downregulated in GBM, in association with a shorter patient survival. In vitro, it negatively regulates cell migration and invasion through the negative regulation of its direct targets IQGAP1, laminin 1, and integrin β1. In vivo, it inhibits glioma invasion by targeting SNAI2. It inhibits glioma stem cell traits through SNAI2 and promotes neuronal differentiation, antagonizing the transcriptional repressor RE1 silencing transcription factor (REST). | |
miR-137 | It is downregulated in GBM and acts as a tumor suppressor. In vitro, it negatively regulates glioma cell migration, invasion, and proliferation, reducing MMP-9 levels and directly targeting Cox-2 expression. | [116] |
miR-145 | Not clear yet. Suggested as pro-invasive oncogene by Koo et al. [124] but as a tumor suppressor inhibiting glioma cell invasion by Lee et al. [123]. | |
miR-146b | Acts as a tumor suppressor. Represses both EGFR and MMP expression, reducing glioma cell migration and invasion. | |
miR-195 | Acts as a tumor suppressor. It is downregulated in GBM, where it promotes proliferation and invasion through deregulation of its targets E2F3 and cyclin D3, respectively. | [119] |
miR- 221/222 | Act as oncogenes: their overexpression in glioma cells causes downregulation of connexin 43, a major component of gap junctions, inducing cell proliferation and invasion. Their overexpression is induced by de-regulated NF-κB and c-Jun transcription factors, resulting in the repression of the cell cycle inhibitor p27kip1 and in the activation of the Akt pathway leading to, among several targets, MMP activation and thus promoting glioma cell proliferation and invasion. | |
miR-302/367 | Act as a tumor suppressor: when expressed, they suppress stemness gene signature, CSC self-renewal, infiltration, and tumorigenic capacity through a drastic inhibition of the CXCR4 pathway (Fareh et al. [120]). | [120] |
miR-410 | Acts as tumor suppressor in GBM, decreasing cell proliferation and invasion by targeting MET and consequently AKT signaling and MMP-9 levels. | [122] |