DNA代谢相关基因的上调与胶质母细胞瘤的放射耐药有关。

Q1 Medicine
Human Gene Therapy Clinical Development Pub Date : 2019-06-01 Epub Date: 2019-03-11 DOI:10.1089/humc.2018.251
Chen Wang, Wang Zheng, Dan Yao, Qianping Chen, Lin Zhu, Junlin Zhang, Yan Pan, Jianghong Zhang, Chunlin Shao
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引用次数: 6

摘要

胶质母细胞瘤是最常见的脑肿瘤,预后较差。放疗是GBMs患者的重要治疗策略;然而,由于GBMs的辐射耐药性,这种治疗仍然是治标不治本的。胶质瘤干细胞(Glioma stem cells, GSCs)作为一个位于细胞层级顶端的亚群,被认为是GBMs放射耐药和复发的关键群体。为了了解GSCs辐射抗性的关键基因,我们从gene expression Omnibus下载GSE54660和GSE60921基因表达谱,进行遗传和转录组学分析,以确定GSCs和GBMs之间潜在的生物标记基因差异表达。然后通过响应辐射的GSCs基因谱对这些候选基因进行筛选,筛选出耐辐射生物标志物基因,包括DNAJC9、GINS2、STAT1、CHAC2、MT1M和ZNF226。将辐照后GSCs中差异表达基因提交基因本体(Gene Ontology, GO)进行富集分析和蛋白-蛋白相互作用(protein-protein interaction, PPI)网络分析。最终选择了一个与GINS2相关的重要模块,并鉴定了一系列参与DNA代谢的基因。总之,本研究提出了一组新的基因,这些基因在GBMs内的放射耐药亚群中差异表达,可能成为有希望的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Upregulation of DNA Metabolism-Related Genes Contributes to Radioresistance of Glioblastoma.

Glioblastomas (GBMs) are the most prevalent brain tumor and exhibit poor prognosis. Radiotherapy is an important strategy for GBMs patients; however, this care remains palliative because of GBMs' radioresistance. Glioma stem cells (GSCs), as a subpopulation residing at the apex of the hierarchy, have been believed to be a pivotal population in radioresistance and recurrence of GBMs. To know the key genes involved in radioresistance of GSCs, the gene expression profiles of GSE54660 and GSE60921 were downloaded from Gene Expression Omnibus for genetic and transcriptomic analysis to identify the potential biomarker genes differentially expressed between GSCs and GBMs. These candidate genes were then filtered by the GSCs gene profile responding to radiation and the radioresistant biomarker genes including DNAJC9, GINS2, STAT1, CHAC2, MT1M, and ZNF226 were screened. The differentially expressed genes in GSCs post-irradiation were submitted to Gene Ontology (GO) for further enrichment analysis and protein-protein interaction (PPI) network analysis. A significant module correlated with GINS2 was finally chosen and a series of genes participating in DNA metabolism were identified. In conclusion, this study propounds a set of novel genes that are differentially expressed in the radioresistant subpopulation within GBMs and could serve as promising therapeutic targets.

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来源期刊
Human Gene Therapy Clinical Development
Human Gene Therapy Clinical Development CRITICAL CARE MEDICINEMEDICINE, RESEARCH &-MEDICINE, RESEARCH & EXPERIMENTAL
CiteScore
7.20
自引率
0.00%
发文量
0
期刊介绍: Human Gene Therapy (HGT) is the premier, multidisciplinary journal covering all aspects of gene therapy. The Journal publishes important advances in DNA, RNA, cell and immune therapies, validating the latest advances in research and new technologies.
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