Glioma is a malignant tumor that affects all kinds of people all over the world. It demonstrates remarkable infiltrative and invasive features. The high expression of interleukin-13 receptor subunit alpha-2 (IL-13Rα2) reportedly plays a pivotal role in some cancers. However, whether IL-13Rα2 contributes to glioma remains unknown. This study demonstrates that IL-13Rα2 is significantly up-regulated in human glioma tissue samples. It is also associated with late stages of disease progression and diminished survival in glioma patients. Gain- and loss-of-function studies demonstrate that IL-13Rα2 promotes the growth, migration, and invasion of glioma cells. In addition, mechanistic investigations show that IL-13Rα2 activates Scr, phosphatidylinositol 3 kinase (PI3K), Akt, and mTOR. Also, restraining Scr in glioma cells attenuates the activation of Scr/PI3K/Akt/mTOR pathway by IL-13Rα2, whereas the silencing of Scr markedly rescues the pro-invasive effect of IL-13Rα2. In conclusion, our results suggest that the high expression of IL-13Rα2 is significantly associated with the growth and metastasis of human glioma cells via the Scr/PI3K/Akt/mTOR pathway, while IL-13Rα2 may be a potential therapeutic target for glioma treatment.
BackgroundNeural stem cells are reported to exist in the hippocampus of adult mammals and are important sources of neurons for repair. The Notch1 signaling pathway is considered as one of the important regulators of neural stem cells, but its role in adult brains is unclear. We aimed to describe the role of Notch1 signaling in the adult rat hippocampus after traumatic brain injury.Material/MethodsThe model rats were randomly divided into 4 groups as follows: sham, sham-TBI, sham-Ad-TBI, and NICD-Ad-TBI. We used adenovirus-mediated gene transfection to upregulate endogenous NICD in vivo. Firstly, a TBI rat model was constructed with lateral fluid percussion. Then, the hippocampus was collected to detect the expression of Notch1 markers and stem cell markers (DCX) by Western blot analysis, immunohistochemistry, and immunofluorescence. The prognosis after TBI treatment was evaluated by the Morris Water Maze test.ResultsFirst, we found the expression of NICD in vivo was significantly increased by adenovirus-mediated gene transfection as assessed by Notch1 immunofluorescence and Western blot analysis. Second, enhancing NICD stimulated the regeneration of neural stem cells in the DG of the adult rat brain following traumatic brain injury, as evaluated by DCX and NeuN double-staining. Furthermore, Notch1 signaling activation can promote behavioral improvement after traumatic brain injury, including spatial learning and memory capacity.ConclusionsOur findings suggest that targeted regulation of Notch1 signaling may have a useful effect on stem cell transformation. Notch1 signaling may have a potential brain-protection effect, which may result from neurogenesis.
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Malignant gliomas are the most prevalent malignancy of the brain. However, there is still lack of
sensitive and accurate biomarkers for gliomas. In this study, we focused on exploring gliomas specific
expressed genes as biomarkers. We evaluated whole-genome genes expression levels in 19 different types of
human cancers by analyzing The Cancer Genome Atlas (TCGA) dataset. A total of 698 gliomas specific
expressed genes were identified. A protein-protein interacting network was constructed to reveal the potential
roles of these gliomas specific genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene
Ontology (GO) analysis showed gliomas specific expressed genes were involved in regulating neuroactive
ligand-receptor interaction, retrograde endocannabinoid signaling, Glutamatergic synapse, chemical synaptic
transmission, nervous system development, central nervous system development, and learning. Of note,
GRIA1, GNAO1, GRIN1, CACNA1A, CAMK2A, and SYP were identified to be down-regulated and
associated with poor prognosis in gliomas. Loss of function assay showed that GNAO1 knockdown
significantly promoted U87 cell proliferation and cell cycle progression. We thought this study will provide
novel biomarkers for gliomas.
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