Abstract
BackgroundGlioma is the most common primary central nervous system tumor derived from glial cells. Kininogen-1 (KNG1) can exert antiangiogenic properties and inhibit proliferation of endothelial cells. The effect of KNG1 on the glioma is rarely reported, so our purpose in to explore its mechanism in glioma cells.MethodsThe differentially expressed genes (DEGs) were identified based on The Cancer Genome Atlas (TCGA) database. The KNG1-vector was transfected into the two glioma cells. The viability, apoptosis and cell cycle of glioma cells and microvessel density (MVD) were detected by cell counting kit-8 assay, flow cytometry and immunohistochemistry, respectively. The expression were measured by quantitative real-time PCR and Western blot, respectively. A tumor mouse model was established to determine apoptosis rate of brain tissue by terminal deoxynucleotidyl transfer-mediated dUTP nick end labeling (TUNEL) analysis.ResultsKNG1 was identified as the core gene and lowly expressed in the glioma cells. Overexpression of KNG1 inhibited cell viability and angiogenesis of glioma cells. Overexpression of KNG1 promoted the apoptosis and G1 phase cell cycle arrest of glioma cells. Moreover, the expressions of VEGF, cyclinD1, ki67, caspase-3/9 and XIAP were regulated by overexpression of KNG1. In addition, overexpression of KNG1 inhibited the activity of PI3K/Akt. Furthermore, overexpression of KNG1 decreased the tumor growth and promoted the apoptosis of decreased by overexpression of KNG1 in vivo. .ConclusionsOverexpression of KNG1 suppresses glioma progression by inhibiting the proliferation and promoting apoptosis of glioma cells, providing a therapeutic strategy for the malignant glioma.
Highlights
Glioma is the most common primary central nervous system tumor derived from glial cells
Identification of differentially expressed genes (DEGs) In our study, the heatmap revealed that 2930 DEGs were identified with The Cancer Genome Atlas (TCGA) dataset and 1591 DEGs were down-regulated while 1439 DEGs were up-regulated (Fig. 1a)
GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of KNG1 The KNG1 was enriched in extracellular exosome, plasma membrane and neuropiptide signaling pathway, suggesting that KNG1 was mainly involved in exocrine function and blood disease (Fig. 1e)
Summary
Glioma is the most common primary central nervous system tumor derived from glial cells. The effect of KNG1 on the glioma is rarely reported, so our purpose in to explore its mechanism in glioma cells. Rapid tumor development and resistance to both chemotherapy and radiotherapy are common in GBM [5], leading to a low 1-year survival rate [10, 11]. It remains to explore the molecular mechanisms on glioma progression and to seek new effective therapeutic strategies of glioma
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