Tripartite motif-containing 25 facilitates immunosuppression and inhibits apoptosis of glioma via activating NF-κB

Exp Biol Med (Maywood). 2022 Sep;247(17):1529-1541. doi: 10.1177/15353702221099460. Epub 2022 Jun 20.

Abstract

As a crucial tumor type of the central nervous system, gliomas are characterized by a dismal prognosis. Tripartite motif-containing 25 (TRIM25), an essential E3 ubiquitin ligase, participates in various biological processes. This study sought to demonstrate its functional role in gliomas. Data obtained from publicly available databases - including The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), and the Repository for Molecular Brain Neoplasia Data (REMBRANDT) - were employed. TRIM25 expression pattern and its association with different clinical characteristics were analyzed. Kaplan-Meier analysis was utilized to compare different TRIM25 expressions with glioma patients' survival. Subsequently, we performed bioinformatic analyses to investigate the biological functions of TRIM25, which were further validated by in vitro experiments, CIBERSORT algorithm, and ESTIMATE evaluation. TRIM25 expression was upregulated in glioma patients and can predict an unfavorable prognosis. Bioinformatic results indicated the involvement of TRIM25 in apoptosis and immune regulation. TRIM25 was associated with programmed death-ligand 1 (PD-L1) related and macrophage-induced immune suppression in gliomas. Meanwhile, silencing TRIM25 promoted apoptosis in glioma cells, which is attributed to its regulation of NF-κB. Therefore, TRIM25 contributed to the glioma malignant progression and suppressive immune microenvironments via NF-κB activation, which may play a therapeutic role in gliomas.

Keywords: NF-κB; TRIM25; apoptosis; glioma; immune suppression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • B7-H1 Antigen
  • Glioma* / metabolism
  • Humans
  • Immunosuppression Therapy
  • NF-kappa B* / metabolism
  • Transcription Factors* / metabolism
  • Tripartite Motif Proteins* / metabolism
  • Tumor Microenvironment
  • Ubiquitin-Protein Ligases* / metabolism

Substances

  • B7-H1 Antigen
  • NF-kappa B
  • Transcription Factors
  • Tripartite Motif Proteins
  • TRIM25 protein, human
  • Ubiquitin-Protein Ligases