Vimentin促进胶质瘤进展并维持胶质瘤细胞抵抗氧化磷酸化抑制。

IF 4.9 2区 医学 Q2 CELL BIOLOGY
Cellular Oncology Pub Date : 2023-12-01 Epub Date: 2023-08-30 DOI:10.1007/s13402-023-00844-3
Yu'e Liu, Shu Zhao, Yi Chen, Wencong Ma, Shiping Lu, Le He, Jie Chen, Xi Chen, Xiaoling Zhang, Yufeng Shi, Xuan Jiang, Kaijun Zhao
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引用次数: 2

摘要

目的:胶质瘤是恶性程度最高的颅内肿瘤之一,目前尚无有效的治疗方法。基于我们之前氧化磷酸化(OXPHOS)抑制抵抗和OXPHOS抑制敏感癌细胞的rna测序数据,我们发现vimentin (VIM)在氧化磷酸化(OXPHOS)抑制抵抗的癌细胞中高表达,特别是在胶质瘤癌细胞中。文献中对VIM的进一步研究表明,VIM在肿瘤进展、免疫治疗抑制、癌变和耐药等方面发挥着重要作用。然而,它在胶质瘤中的作用仍然难以捉摸。本研究旨在揭示VIM在胶质瘤中的作用,特别是其在oxphos抑制敏感性中的作用,为胶质瘤的治疗提供一个有希望的治疗靶点。方法:从Cancer Genome Atlas (TCGA)数据库中获取VIM在胶质瘤和正常组织中的表达,并在Human Protein Atlas (HPA)和Chinese glioma Genome Atlas (CGGA)中进一步验证。单细胞测序数据来源于TISCH2。通过肿瘤免疫估计资源(Tumor immune Estimation Resource, TIMER)计算免疫浸润,使用表达数据(ESTIMATE)和ssGSEA计算恶性肿瘤基质和免疫细胞,通过R包计算免疫表型(Immunophenoscore, IPS)。通过GO/KEGG和基因集富集分析(GSEA)对vim高、低组间的差异表达基因进行分析。通过EWAS和Methsurv检测VIM的甲基化。VIM表达与癌干性的相关性由SangerBox获得。我们还利用DepMap数据,通过在VIM-高胶质瘤细胞中敲低VIM,在VIM-低胶质瘤细胞中过表达VIM,验证了VIM的作用,检测细胞活力。结果:在胶质瘤患者中,Vim的高表达与患者的生存率呈负相关。胶质瘤患者VIM启动子的DNA甲基化水平低于正常样本。VIM高表达与免疫浸润和肿瘤进展呈正相关。此外,Vim在oxphos抑制胶质瘤细胞中高表达,在oxphos抑制敏感细胞中低表达,其表达维持了oxphos抑制的抗性。结论:我们全面解读了VIM在胶质瘤进展及其临床结局中的作用。从而为以VIM为靶点的神经胶质瘤免疫治疗与当前治疗相结合提供了新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Vimentin promotes glioma progression and maintains glioma cell resistance to oxidative phosphorylation inhibition.

Vimentin promotes glioma progression and maintains glioma cell resistance to oxidative phosphorylation inhibition.

Purpose: Glioma has been demonstrated as one of the most malignant intracranial tumors and currently there is no effective treatment. Based on our previous RNA-sequencing data for oxidative phosphorylation (OXPHOS)-inhibition resistant and OXPHOS-inhibition sensitive cancer cells, we found that vimentin (VIM) is highly expressed in the OXPHOS-inhibition resistant cancer cells, especially in glioma cancer cells. Further study of VIM in the literature indicates that it plays important roles in cancer progression, immunotherapy suppression, cancer stemness and drug resistance. However, its role in glioma remains elusive. This study aims to decipher the role of VIM in glioma, especially its role in OXPHOS-inhibition sensitivity, which may provide a promising therapeutic target for glioma treatment.

Methods: The expression of VIM in glioma and the normal tissue has been obtained from The Cancer Genome Atlas (TCGA) database, and further validated in Human Protein Atlas (HPA) and Chinese Glioma Genome Atlas (CGGA). And the single-cell sequencing data was obtained from TISCH2. The immune infiltration was calculated via Tumor Immune Estimation Resource (TIMER), Estimation of Stromal and Immune Cells in Malignant Tumors using Expression Data (ESTIMATE) and ssGSEA, and the Immunophenoscore (IPS) was calculated via R package. The differentiated expressed genes were analyzed including GO/KEGG and Gene Set Enrichment Analysis (GSEA) between the VIM-high and -low groups. The methylation of VIM was checked at the EWAS and Methsurv. The correlation between VIM expression and cancer stemness was obtained from SangerBox. We also employed DepMap data and verified the role of VIM by knocking down it in VIM-high glioma cell and over-expressing it in VIM-low glioma cells to check the cell viability.

Results: Vim is highly expressed in the glioma patients compared to normal samples and its high expression negatively correlates with patients' survival. The DNA methylation in VIM promoters in glioma patients is lower than that in the normal samples. High VIM expression positively correlates with the immune infiltration and tumor progression. Furthermore, Vim is expressed high in the OXPHOS-inhibition glioma cancer cells and low in the OXPHOS-inhibition sensitive ones and its expression maintains the OXPHOS-inhibition resistance.

Conclusions: In conclusion, we comprehensively deciphered the role of VIM in the progression of glioma and its clinical outcomes. Thus provide new insights into targeting VIM in glioma cancer immunotherapy in combination with the current treatment.

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来源期刊
Cellular Oncology
Cellular Oncology ONCOLOGY-CELL BIOLOGY
CiteScore
10.30
自引率
1.50%
发文量
86
审稿时长
12 months
期刊介绍: The Official Journal of the International Society for Cellular Oncology Focuses on translational research Addresses the conversion of cell biology to clinical applications Cellular Oncology publishes scientific contributions from various biomedical and clinical disciplines involved in basic and translational cancer research on the cell and tissue level, technical and bioinformatics developments in this area, and clinical applications. This includes a variety of fields like genome technology, micro-arrays and other high-throughput techniques, genomic instability, SNP, DNA methylation, signaling pathways, DNA organization, (sub)microscopic imaging, proteomics, bioinformatics, functional effects of genomics, drug design and development, molecular diagnostics and targeted cancer therapies, genotype-phenotype interactions. A major goal is to translate the latest developments in these fields from the research laboratory into routine patient management. To this end Cellular Oncology forms a platform of scientific information exchange between molecular biologists and geneticists, technical developers, pathologists, (medical) oncologists and other clinicians involved in the management of cancer patients. In vitro studies are preferentially supported by validations in tumor tissue with clinicopathological associations.
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