Yang Quanxi, Deng Lei, Li Jialiang, Miao Pengfei, Liu Wenxiang, Huang Qi
Department of Neurosurgery, The First People's Hospital of Shangqiu in Henan Province, Shangqiu Clinical College, Xuzhou Medical University, Shangqiu 476100, People's Republic of China.
Department of Neonatology, The First People's Hospital of Shangqiu in Henan Province, Shangqiu Clinical College, Xuzhou Medical University, Shangqiu 476100, People's Republic of China.
Onco Targets Ther. 2020 Oct 12;13:10231-10244. doi: 10.2147/OTT.S243833. eCollection 2020.
Glioma is a fatal primary malignant tumor. We aimed to explore the effect of nuclear receptor subfamily 5 group A member 2 () on glioma.
expression in glioma tissues and cells was detected using qRT-PCR and immunohistochemistry (IHC)/Western blot. SPSS 22.0 was performed to explore the relationship between expression and glioma clinicopathologic features. The down-expressed plasmid of was transfected into glioma cells, and the cell viability, proliferation, apoptosis, migration, and invasion were respectively determined by MTT, EdU, flow cytometry, wound healing and transwell assays. Cell cycle was analyzed using flow cytometry. Temozolomide (TMZ)-resistant glioma cells were established to define the effect of on drug resistance. The expressions of Notch pathway-related proteins were assessed by Western blot. Glioma nude mice model was constructed to explore the role of played in vivo.
was highly expressed in glioma tissues and cell lines. overexpression was related to the poor prognosis of glioma patients. knockdown inhibited cell viability, proliferation, migration, and invasion, induced cell cycle arrest and promoted cell apoptosis in U138 and U251 cells. In U138/TMZ and U251/TMZ cell lines, upregulation enhanced TMZ resistance while downregulation reduced it. The knockdown of influenced the expressions of Notch pathway-related proteins. knockdown suppressed tumor growth and facilitated apoptosis in glioma mice model.
affected glioma cell malignant behaviors and TMZ resistance via Notch signaling pathway and it might be a novel target in glioma therapy.
胶质瘤是一种致命的原发性恶性肿瘤。我们旨在探讨核受体亚家族5组A成员2（）对胶质瘤的影响。
采用qRT-PCR和免疫组织化学（IHC）/蛋白质免疫印迹法检测胶质瘤组织和细胞中的表达。运用SPSS 22.0软件探讨表达与胶质瘤临床病理特征之间的关系。将的低表达质粒转染到胶质瘤细胞中，分别通过MTT法、EdU法、流式细胞术、伤口愈合实验和Transwell实验测定细胞活力、增殖、凋亡、迁移和侵袭能力。采用流式细胞术分析细胞周期。建立替莫唑胺（TMZ）耐药的胶质瘤细胞，以确定对耐药性的影响。通过蛋白质免疫印迹法评估Notch信号通路相关蛋白的表达。构建胶质瘤裸鼠模型，以探讨在体内发挥的作用。
在胶质瘤组织和细胞系中高表达。的过表达与胶质瘤患者的不良预后相关。敲低可抑制U138和U251细胞的活力、增殖、迁移和侵袭，诱导细胞周期阻滞并促进细胞凋亡。在U138/TMZ和U251/TMZ细胞系中，上调增强TMZ耐药性，而下调则降低耐药性。敲低影响Notch信号通路相关蛋白的表达。敲低可抑制胶质瘤小鼠模型中的肿瘤生长并促进细胞凋亡。
通过Notch信号通路影响胶质瘤细胞的恶性行为和TMZ耐药性，可能是胶质瘤治疗的一个新靶点。
