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已撤稿:锌指蛋白 207 通过调控上皮-间质转化协调胶质瘤迁移

英文原题:RETRACTED: Zinc finger Protein207 orchestrates glioma migration through regulation of epithelial-mesenchymal transition.

查看英文原题

RETRACTED: Zinc finger Protein207 orchestrates glioma migration through regulation of epithelial-mesenchymal transition.

PubMed 2024/04/09(内容时间) Environ Toxicol

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研究概要

ZNF207 可能被确定为胶质瘤预防的前瞻性生物标志物和治疗候选靶点,为理解胶质瘤发病机制和治疗策略提供有价值的见解。

研究思路结论见上方概要

胶质瘤是最常见的原发性恶性脑肿瘤。多年来,分子分型在胶质瘤的管理和治疗分层中发挥了重要作用,使人们对其生物学复杂性有了更深入的理解。越来越多的证据揭示了锌指蛋白(ZNFs)在癌症中的潜在参与。本研究旨在阐明ZNF207在胶质瘤中的作用和意义。

利用癌症基因组图谱(TCGA)、中国脑胶质瘤基因组图谱(CGGA)、基因型-组织表达(GTEx)计划、临床蛋白质组肿瘤分析联盟(CPTAC)和人类蛋白质图谱(HPA)数据库等在线数据,结合GO、KEGG、GSEA、CIBERSORT免疫细胞浸润估计和蛋白质-蛋白质相互作用(PPI)分析等生物信息学方法,全面探索了ZNF207在胶质瘤发生中的参与。采用免疫组织化学和RT-PCR技术验证ZNF207在胶质瘤样本中的表达水平。随后,通过体外实验探讨了ZNF207对胶质瘤细胞的生物学效应。

我们的结果证明ZNF207在胶质瘤中表达升高,与患者不良预后相关。分层分析用于描述ZNF207在不同临床病理特征胶质瘤中的预后效能。免疫相关性分析显示ZNF207表达与T辅助细胞、巨噬细胞和自然杀伤(NK)细胞的浸润水平显著相关。利用ZNF207表达和临床特征,我们构建了OS预测模型,并显示出良好的区分能力,C-index为0.861。此外,策略性沉默ZNF207减弱了胶质瘤细胞的进展,表现为细胞增殖减少、细胞致瘤性减弱、凋亡活性增强、迁移能力受限,同时抑制了上皮-间质转化(EMT)通路。

展开英文摘要原文

Glioma represents the predominant primary malignant brain tumor. For several years, molecular profiling has been instrumental in the management and therapeutic stratification of glioma, providing a deeper understanding of its biological complexity. Accumulating evidence unveils the putative involvement of zinc finger proteins (ZNFs) in cancer. This study aimed to elucidate the role and significance of ZNF207 in glioma.

Utilizing online data such as The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), the Genotype-Tissue Expression (GTEx) project, the Clinical Proteomic Tumor Analysis Consortium (CPTAC), and the Human Protein Atlas (HPA) databases, in conjunction with bioinformatics methodologies including GO, KEGG, GSEA, CIBERSORT immune cell infiltration estimation, and protein-protein interaction (PPI) analysis, enabled a comprehensive exploration of ZNF207's involvement in gliomagenesis. Immunohistochemistry and RT-PCR techniques were employed to validate the expression level of ZNF207 in glioma samples. Subsequently, the biological effects of ZNF207 on glioma cells were explored through in vitro assays.

Our results demonstrate elevated expression of ZNF207 in gliomas, correlating with unfavorable patient outcomes. Stratification analyses were used to delineate the prognostic efficacy of ZNF207 in glioma with different clinicopathological characteristics. Immunocorrelation analysis revealed a significant association between ZNF207 expression and the infiltration levels of T helper cells, macrophages, and natural killer (NK) cells. Utilizing ZNF207 expression and clinical features, we constructed an OS prediction model and displayed well discrimination with a C-index of 0.861. Moreover, the strategic silencing of ZNF207 attenuated glioma cell advancement, evidenced by diminished cellular proliferation, weakened cell tumorigenesis, augmented apoptotic activity, and curtailed migratory capacity alongside the inhibition of the epithelial-mesenchymal transition (EMT) pathway.

ZNF207 may identify as a prospective biomarker and therapeutic candidate for glioma prevention, providing valuable insights into understanding glioma pathogenesis and treatment strategies.

论文信息

作者
Zhao C、Guo Y、Chen Y、Shang G、Song D、Wang J、Yang J、Zhang H
单位
Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, China.China
文献类型
已撤稿
期刊
Environmental toxicology2025 May
原文标识
PubMed 38591780 · DOI 10.1002/tox.24271