Furthermore, induced overexpression of miR-490-3p in GBM cell lines significantly inhibited key hallmarks including cellular proliferation, colony formation and spheroid formation, as well as epithelial-to-mesenchymal transition (EMT), with downregulation of multiple EMT transcription factors and promigratory genes (MMP9, CCL5, PIK3R1, ICAM1, ADAM17 and NOTCH1).
In this study, we validated that Notch1 and NF-κB(p65) are highly expressed in the classical and proneural subtypes of GBM using the data set from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA).
In conclusion, the results of the present study suggested that upregulation of Notch1 is involved in the chemotherapy resistance and tumor recurrence of glioblastoma.
Of note, we identified a function for S518-Merlin, which is distinct from what has been reported when the expression of Merlin is diminished in relation to EGFR and NOTCH1 expression, providing first-time evidence that demonstrates that the phosphorylation of S518-Merlin in glioblastoma promotes oncogenic properties that are not only the result of inactivation of the tumor suppressor role of Merlin but also an independent process implicating a Merlin-driven regulation of NOTCH1 and EGFR.
A functional polymorphism in the pre‑miR‑146a gene influences the prognosis of glioblastoma multiforme by interfering with the balance between Notch1 and Notch2.
To determine the clinical importance of Notch-1 expression in glioblastoma, we analyzed 15 patients who had received bevacizumab therapy followed by a second surgery at recurrence.
We had knocked down Notch1 by siRNA in glioblastoma cells, and identified that the cell growth and invasion were inhibited, whereas cell apoptosis was induced either in vitro or in vivo.
Morphological analysis confirmed inhibition of NICD when U251 MG cells were treated with puPA, puPAR or pU2. uPA/uPAR down regulation inhibited Notch 1 mRNA in all three examined cell lines. uPA/uPAR shRNA down regulated nuclear activation of NF-κB subunits and phosphorylation of AKT/mTOR pathway in U251 MG and GBM xenografts. puPA down regulated NICD and HES induced phosphorylation of AKT/ERK and NF-κB.
In this study, we quantified RNA expression levels of stem cell markers [CD133, Nestin, BMI-1, maternal embryonic leucine zipper kinase (MELK), and Notch1-4] as well as RTKs (EGFR, ErbB4, VEGFR1-3, FGFR1, -2, PDGFRΑ, and PDGFRΒ) in 42 clinical samples of glioblastoma by the real-time RT-PCR method.
Taken together, we confirmed the anti-proliferative and pro-apoptotic effects of resveratrol on glioblastoma cells and revealed Notch-1 activation-dependent restoration of p53 as an important causative mechanism.
Knockdown of individual Notch receptors revealed that Notch1 and Notch2 receptors differentially contributed to GBM cell growth, with Notch2 having a predominant role.