Vimentin Promotes Glioma Progression and Maintains Glioma Cell Resistance to Oxidative Phosphorylation Inhibition

Authors

• 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

Language

English

Publication Date

12-1-2023

Journal

Cellular Oncology

DOI

10.1007/s13402-023-00844-3

PMID

37646965

PMCID

PMC12974705

PubMedCentral® Posted Date

8-30-2023

PubMedCentral® Full Text Version

Post-print

Abstract

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.

Keywords

Humans, Brain Neoplasms, DNA Methylation, Glioma, Oxidative Phosphorylation, Vimentin, Vimentin, Glioma, Immune infiltration, Oxidative phosphorylation, Drug resistance

Published Open-Access

yes

Recommended Citation

Liu, Yu'e; Zhao, Shu; Chen, Yi; et al., "Vimentin Promotes Glioma Progression and Maintains Glioma Cell Resistance to Oxidative Phosphorylation Inhibition" (2023). Faculty, Staff and Students Publications. 7048.
https://digitalcommons.library.tmc.edu/baylor_docs/7048