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GRB10是一种与胶质瘤细胞增殖和预后相关的新型癌基因。

GRB10 is a novel oncogene associated with cell proliferation and prognosis in glioma.

作者信息

Chen Yuanbing, Tang Miao, Xiong Jianbing, Gao Qiongjue, Cao Wuyang, Huang Jun

机构信息

Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.

National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.

出版信息

Cancer Cell Int. 2022 Jul 5;22(1):223. doi: 10.1186/s12935-022-02636-5.

Abstract

BACKGROUND

Glioma is the most common malignant tumor of the central nervous system and is associated with a poor prognosis. This study aimed to explore the function of growth factor receptor-bound protein 10(GRB 10) in glioma.

METHODS

The expression of GRB10 in glioma was determined based on the glioma transcriptome profile downloaded from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and Gene Expression Omnibus (GEO) databases. RT-qPCR was performed to detect the expression of GRB10 in tissue samples obtained from 68 glioma patients. The patients were followed up via telephone or in-person outpatient visits to determine survival. Kaplan-Meier survival analyses were used to evaluate the effect of GRB10 on the prognosis of glioma patients. Further, we constructed GRB10 knockdown cell lines were constructed to investigate the effect of GRB10 on glioma. The cell growth, colony formation, cell cycle assay, EdU assay, and tumor formation in xenograft were performed.

RESULTS

The expression level of GRB10 was positively correlated to the histological grades of gliomas. In addition, Kaplan-Meier survival curves revealed that glioma patients with lower expression of GRB10 had more prolonged survival. The knockdown of GRB10 was shown to inhibit cell proliferation, colony formation, and tumor formation in the xenograft models. Cell cycle assay revealed that the knockdown of GRB10 can inhibit the cells entering the G2/M phase from the S phase. The analysis of GSEA suggests that the expression of GRB10 was positively correlated with the hypoxia and EMT signaling pathway.

CONCLUSIONS

Our data revealed that GRB10 regulated tumorigenesis in glioma and played a vital role in promoting the glioma progression, which indicated that GRB10 could be used as a potential prognostic marker.

摘要

背景

胶质瘤是中枢神经系统最常见的恶性肿瘤,预后较差。本研究旨在探讨生长因子受体结合蛋白10(GRB 10)在胶质瘤中的作用。

方法

基于从癌症基因组图谱(TCGA)、中国胶质瘤基因组图谱(CGGA)和基因表达综合数据库(GEO)下载的胶质瘤转录组谱,确定GRB10在胶质瘤中的表达。采用RT-qPCR检测68例胶质瘤患者组织样本中GRB10的表达。通过电话或门诊随访患者以确定生存期。采用Kaplan-Meier生存分析评估GRB10对胶质瘤患者预后的影响。此外,构建GRB10敲低细胞系,以研究GRB10对胶质瘤的影响。进行细胞生长、集落形成、细胞周期分析、EdU分析和异种移植中的肿瘤形成实验。

结果

GRB10的表达水平与胶质瘤的组织学分级呈正相关。此外,Kaplan-Meier生存曲线显示,GRB10表达较低的胶质瘤患者生存期更长。GRB10敲低可抑制异种移植模型中的细胞增殖、集落形成和肿瘤形成。细胞周期分析显示,GRB10敲低可抑制细胞从S期进入G2/M期。GSEA分析表明,GRB10的表达与缺氧和EMT信号通路呈正相关。

结论

我们的数据表明,GRB10在胶质瘤中调节肿瘤发生,在促进胶质瘤进展中起重要作用,这表明GRB10可作为潜在的预后标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/380e/9254544/4cdff3f22df0/12935_2022_2636_Fig1_HTML.jpg

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