Impact of endogenous viral elements on glioma clinical phenotypes by inducing OCT4 in the host

Front Cell Infect Microbiol. 2024 Nov 11:14:1474492. doi: 10.3389/fcimb.2024.1474492. eCollection 2024.

Abstract

Introduction: Endogenous viral elements (EVEs) are viral sequences integrated within the host genome that can influence gene regulation and tumor development. While EVEs have been implicated in cancer, their role in regulating key transcription factors in glioblastoma (GBM) remains underexplored. This study investigates the relationship between EVEs and the activation of OCT4, a critical transcription factor in GBM progression.

Methods: We utilized CancerHERVdb and HervD Atlas databases to identify potential interactions between EVEs and key genes involved in GBM. Data from 273 GBM patient samples in the TCGA database were analyzed to examine the correlation between OCT4 expression and mutations in glioma-related genes. Furthermore, glioblastoma stem cells (GSCs) were assessed for the expression levels of OCT4 and SOX2, and Pearson correlation analysis was performed.

Results: Our analysis revealed that OCT4 is a pivotal gene activated by EVEs in GBM. OCT4 expression was significantly correlated with mutations in key glioma-associated genes. Higher OCT4 levels were associated with poorer patient prognosis, higher tumor grades, and older age. Additionally, GSCs exhibited elevated expression of both OCT4 and SOX2, with a positive correlation observed between these two genes in GBM patients.

Discussion: This study highlights the potential role of EVEs in driving GBM progression through the activation of OCT4. The findings emphasize the importance of OCT4 in GBM malignancy and suggest that targeting EVE-mediated pathways may provide new therapeutic approaches for GBM treatment.

Keywords: OCT4; RNA; endogenous viral elements; glioblastoma; glioblastoma stem cells; transcription factors.

MeSH terms

  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Brain Neoplasms / virology
  • Endogenous Retroviruses / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma / genetics
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Glioblastoma / virology
  • Glioma* / genetics
  • Glioma* / metabolism
  • Glioma* / pathology
  • Glioma* / virology
  • Humans
  • Mutation
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / virology
  • Octamer Transcription Factor-3* / genetics
  • Octamer Transcription Factor-3* / metabolism
  • Phenotype
  • Prognosis
  • SOXB1 Transcription Factors* / genetics
  • SOXB1 Transcription Factors* / metabolism

Substances

  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • SOXB1 Transcription Factors
  • SOX2 protein, human

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The study was supported by Shenzhen Key Medical Discipline Construction Fund (No. SZGSP002) and Sanming Project of Medicine in Shenzhen (No. SZSM202011018).