CENPF as a prognostic marker of glioma: unraveling the molecular mechanisms.

IF 2.7 3区 医学 Q3 ONCOLOGY
Xiuyang Chen, Yiwei Wu, Yining Xing, Peng Zhong
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引用次数: 0

Abstract

Objective: Glioma is the dominant primary intracranial malignancy. The roles of CENPF and the CENPF - p53 axis in glioma remain elusive. This study uses bioinformatics and animal experiments to clarify the relationship between CENPF and p53 in glioma. CENPF affects spindle assembly and chromosomal segregation, while p53 is a tumor-suppressor gene. Their dysregulation may interact and impact glioma development. Our research aims to uncover the underlying molecular mechanisms, offering new perspectives for glioma diagnosis and treatment.

Method: Gene expression data from the Gene Expression Omnibus (GEO) database ( http://www.ncbi.nlm.nih.gov/geo/ ) were retrieved, specifically datasets GSE50161, GSE104291, and GSE12249. Volcano plots were generated to visualize differentially expressed genes (DEGs), and intersecting DEGs were identified using Venn diagrams. Weighted gene co-expression network analysis (WGCNA) was employed to construct and analyze the protein-protein interaction (PPI) network. Additionally, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted. Gene set enrichment analysis (GSEA) was utilized for comprehensive GO and KEGG analyses of the entire genome. Comparative Toxicogenomics Database (CTD) analysis was performed, and TargetScan was used to identify miRNAs regulating central DEGs. An animal model of glioma was established and analyzed via Western blot.

Result: A total of 501 differentially expressed genes (DEGs) were identified, from which eight significant modules were generated and ten core genes were extracted. These core genes exhibited differential expression patterns between glioma tumor and non-tumor samples. Expression analysis revealed that the ten core genes associated with glioma (CENPF, PBK, ASPM, KIF2C, KIF20A, CDC20, TOP2A, NUSAP1, TTK, KIF23) were significantly upregulated in tumor tissues (P < 0.05). They are primarily enriched in protein signal transduction, coated membrane structures, AP-type membrane coat adaptor complexes, and chloride channel activity. KEGG pathway analysis indicated that these target genes were mainly involved in nicotine addiction, arginine and proline metabolism, beta-alanine metabolism, and histidine metabolism. The mouse model confirmed that CENPF and CDK-1 were highly expressed in glioma tissues, while p53, p21, and Caspase9 were downregulated, leading to inhibition of the apoptosis pathway and exacerbation of glioma progression. Overexpression of CENPF further suppressed key molecules in the p53-mediated apoptosis pathway. Conversely, low expression of CENPF activated these key molecules, inducing apoptosis in glioma cells.

Conclusions: CENPF exhibits elevated expression levels in glioma, potentially inhibiting cell apoptosis via the p53 signaling pathway, consequently contributing to the onset and progression of glioma.

CENPF作为胶质瘤的预后标志物:揭示分子机制。
目的:胶质瘤是颅内主要的原发性恶性肿瘤。CENPF和CENPF - p53轴在胶质瘤中的作用尚不清楚。本研究采用生物信息学和动物实验的方法来阐明神经胶质瘤中CENPF和p53的关系。CENPF影响纺锤体组装和染色体分离,而p53是一种肿瘤抑制基因。它们的失调可能相互作用并影响胶质瘤的发展。我们的研究旨在揭示其潜在的分子机制,为胶质瘤的诊断和治疗提供新的视角。方法:从Gene expression Omnibus (GEO)数据库(http://www.ncbi.nlm.nih.gov/geo/)检索基因表达数据,具体数据集为GSE50161、GSE104291和GSE12249。生成火山图以显示差异表达基因(deg),并使用维恩图识别交叉的deg。采用加权基因共表达网络分析法(Weighted gene co-expression network analysis, WGCNA)构建并分析蛋白-蛋白相互作用(protein-protein interaction, PPI)网络。此外,还进行了基因本体(GO)和京都基因与基因组百科全书(KEGG)途径分析。基因集富集分析(GSEA)用于对整个基因组进行全面的GO和KEGG分析。进行比较毒物基因组学数据库(CTD)分析,并使用TargetScan识别调节中心DEGs的mirna。建立脑胶质瘤动物模型并进行Western blot分析。结果:共鉴定出501个差异表达基因(DEGs),从中产生8个显著模块,提取出10个核心基因。这些核心基因在胶质瘤和非肿瘤样本中表现出不同的表达模式。表达分析显示,与胶质瘤相关的10个核心基因(CENPF、PBK、ASPM、KIF2C、KIF20A、CDC20、TOP2A、NUSAP1、TTK、KIF23)在肿瘤组织中显著上调(P)。结论:CENPF在胶质瘤中表达水平升高,可能通过p53信号通路抑制细胞凋亡,从而参与胶质瘤的发生和发展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
4.00
自引率
2.80%
发文量
577
审稿时长
2 months
期刊介绍: The "Journal of Cancer Research and Clinical Oncology" publishes significant and up-to-date articles within the fields of experimental and clinical oncology. The journal, which is chiefly devoted to Original papers, also includes Reviews as well as Editorials and Guest editorials on current, controversial topics. The section Letters to the editors provides a forum for a rapid exchange of comments and information concerning previously published papers and topics of current interest. Meeting reports provide current information on the latest results presented at important congresses. The following fields are covered: carcinogenesis - etiology, mechanisms; molecular biology; recent developments in tumor therapy; general diagnosis; laboratory diagnosis; diagnostic and experimental pathology; oncologic surgery; and epidemiology.
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