Molecular mechanism of Notch signaling with special emphasis on microRNAs: Implications for glioma

Glioma is the most aggressive primary brain tumor and is notorious for resistance to chemoradiotherapy. Although its associated mechanisms are still not completely understood, Notch signaling, an evolutionarily conserved pathway, appears to be the key processes involved. Nevertheless, its mechanisms are sophisticated, due to a variety of targets and signal pathways, especially microRNA. MicroRNAs, which are small noncoding regulatory RNA molecules, have been proposed as one of the key mechanisms in glioma pathogenesis. Among the known glioma associated microRNA, microRNA‐129, microRNA‐34 family, and microRNA‐326 have been shown to influence the progress of glioma through Notch signaling. Evidence also indicates that recurrence is due to development or persistence of the glioma stem‐like cells and active angiogenesis, which are tightly regulated by a variety of factors, including Notch signaling. In this review, we summarize the recent progress regarding the functional roles of Notch signaling in glioma, including Notch ligand, microRNA, intracellular crosstalk, glioma stem‐like cells and active angiogenesis and explore their clinical implications as diagnostic or prognostic biomarkers and molecular therapeutic targets for glioma. Notch signaling and its ligands act as an oncogene in glioma; microRNAs influence the progress of glioma through Notch signaling; a combination of chemoradiotherapy and disruption of Notch signaling might be a new method of glioma therapy.