首页|LncRNA HOTAIR对胶质母细胞瘤细胞增殖的影响及在临床治疗中的意义

LncRNA HOTAIR对胶质母细胞瘤细胞增殖的影响及在临床治疗中的意义

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目的:探讨在胶质母细胞瘤(GBM)中lncRNA HOTAIR基因表达的生物学价值.方法:利用生物信息学技术挖掘癌症基因组图谱(TCGA)和中国胶质瘤基因组图谱计划(CGGA)的测序及芯片数据,评估HOTAIR 表达水平与GBM患者预后的关系并分析其可能的机制,构建HOTAIR过表达质粒并转染U251人脑胶质瘤细胞系,细胞增殖及克隆实验研究HOTAIR对胶质瘤细胞的作用.利用癌症治疗反应数据库(CTRP)和PRISM数据库中的药敏数据探寻靶向HOTAIR的潜在药物.结果:HOTAIR在GBM中表达明显上调,其表达量越高患者预后越差.过表达HOTAIR显著提高U251细胞的增殖活力.烟酰胺磷酸核糖转移酶抑制剂等9种药物对HOTAIR高表达患者或许具有靶向治疗作用.结论:HOTAIR可能通过调控细胞周期影响GBM患者预后,有可能作为药物治疗的潜在靶点.
Effect of lncRNA HOTAIR on glioblastoma cell proliferation and its significance in clinical therapy
Objective:To investigate the biological values of lncRNA HOTAIR in glioblastoma(GBM),as well as the potential treatment drugs by bioinformatics analysis and experimental research.Methods:The sequencing profile of The Cancer Genome Atlas(TCGA)and the microarray profile of the Chi-nese Glioma Genome Atlas(CGGA)were used to evaluate the association between the HOTAIR ex-pression level and the prognosis of GBM patients,and to analyze the underlying mechanism.The HOTAIR overexpression plasmids were conducted and transfected into U251 cells.The impact of HOTAIR in GBM was verified by cell proliferation and colony formation assays.The drug sensitivity data,which were achieved from the Cancer Therapeutics Response Portal(CTRP)and PRISM Repurposing dataset,were applied to identify the candidate agents targeting HOTAIR.Results:HO-TAIR was significantly upregulated in GBM,and the higher expression of HOTAIR,the worse prog-nosis of GBM patients.Moreover,overexpressed HOTAIR could significantly enhance the prolifera-tion of U251 cells.Nine treatment agents including nicotinamide phosphoribosyltransferase inhibitor could be the target drugs for HOTAIR high expression GBM patients.Conclusion:HOTAIR was as-sociated with GBM patients'prognosis might by regulating the cell cycle process,which could be a po-tential therapeutic target.

HOTAIRGlioblastomaProliferationPrognosisTarget Therapy

兰天、孙翔宇、余东虎、吴嵽、李志强

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武汉大学中南医院神经外科 湖北 武汉 430071

武汉大学中南医院麻醉科 湖北 武汉 430071

HOTAIR 胶质母细胞瘤 细胞增殖 预后 靶向治疗

2024

武汉大学学报(医学版)
武汉大学

武汉大学学报(医学版)

CSTPCD
影响因子:0.959
ISSN:1671-8852
年,卷(期):2024.45(1)
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