The role of DNAJC3 in enhancing glioma progression and regulating the tumor immune microenvironment

TL;DR

DNAJC3 promotes glioma progression and immune evasion, suggesting it could be a new target for treatment.

Contribution

This study identifies DNAJC3 as a novel driver of glioma malignancy and immune suppression.

Findings

DNAJC3 is significantly overexpressed in glioma and contributes to its malignant progression.

DNAJC3 activates MAPK-ERK and PI3K-AKT pathways to exert oncogenic effects.

DNAJC3 may suppress immune cell infiltration and confer resistance to MAP kinase inhibitors.

Abstract

Endoplasmic reticulum stress (ERS) is one of the important characteristics of tumors. Studies have demonstrated that ERS-related proteins play crucial roles in tumor initiation, progression, and immune infiltration. However, the specific role of ERS-induced DNAJC3 (DnaJ heat shock protein family [heat shock protein 40] member C3) in glioma remains unclear. In this study, we employed proteomic profiling combined with public databases to screen for differentially expressed proteins and found that DNAJC3 was significantly overexpressed in glioma. Subsequently, a series of cellular functional experiments were conducted to validate the important role of DNAJC3 in the malignant progression of glioma. In terms of mechanism, we found that DNAJC3 may exert its oncogenic effects by activating the mitogen-activated protein kinase–extracellular signal–regulated kinase and PI3K–AKT signaling pathways. Further in-depth analysis of the relationship between DNAJC3 expression levels and immune cell infiltration in glioma revealed that DNAJC3 may possess immunosuppressive properties. In addition, drug sensitivity analysis suggested that DNAJC3 expression may be associated with resistance to mitogen-activated protein kinase kinase inhibitors in glioma patients. In conclusion, this study found that DNAJC3 may play a significant role in the malignant progression and immune evasion of glioma, suggesting its potential as a therapeutic target. This finding is of great significance for understanding the role of DNAJC3 in the malignant progression of glioma and its oncogenic mechanisms. Moreover, it provides a theoretical basis for further exploring the immune evasion mechanisms of glioma and optimizing personalized treatment strategies.

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