DNAJC1 通过促进细胞外基质重排和巨噬细胞浸润促进胶质母细胞瘤进展。

DNAJC1 facilitates glioblastoma progression by promoting extracellular matrix reorganization and macrophage infiltration.

机构信息

State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi'an, 710032, China.

Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, 710054, China.

出版信息

J Cancer Res Clin Oncol. 2024 Jun 22;150(6):315. doi: 10.1007/s00432-024-05823-1.

DOI:10.1007/s00432-024-05823-1

PMID:38909166

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11193832/

Abstract

BACKGROUND

Glioblastoma (GBM) is a high-grade and heterogeneous subtype of glioma that presents a substantial challenge to human health, characterized by a poor prognosis and low survival rates. Despite its known involvement in regulating leukemia and melanoma, the function and mechanism of DNAJC1 in GBM remain poorly understood.

METHODS

Utilizing data from the TCGA, CGGA, and GEO databases, we investigated the expression pattern of DNAJC1 and its correlation with clinical characteristics in GBM specimens. Loss-of-function experiments were conducted to explore the impact of DNAJC1 on GBM cell lines, with co-culture experiments assessing macrophage infiltration and functional marker expression.

RESULTS

Our analysis demonstrated frequent overexpression of DNAJC1 in GBM, significantly associated with various clinical characteristics including WHO grade, IDH status, chromosome 1p/19q codeletion, and histological type. Moreover, Kaplan‒Meier and ROC analyses revealed DNAJC1 as a negative prognostic predictor and a promising diagnostic biomarker for GBM patients. Functional studies indicated that silencing DNAJC1 impeded cell proliferation and migration, induced cell cycle arrest, and enhanced apoptosis. Mechanistically, DNAJC1 was implicated in stimulating extracellular matrix reorganization, triggering the epithelial-mesenchymal transition (EMT) process, and initiating immunosuppressive macrophage infiltration.

CONCLUSIONS

Our findings underscore the pivotal role of DNAJC1 in GBM pathogenesis, suggesting its potential as a diagnostic and therapeutic target for this challenging disease.

摘要

背景

胶质母细胞瘤（GBM）是一种高级别且异质性的神经胶质瘤亚型，对人类健康构成重大挑战，其预后差，生存率低。尽管已知 DNAJC1 参与调节白血病和黑色素瘤，但在 GBM 中，DNAJC1 的功能和机制仍知之甚少。

方法

利用 TCGA、CGGA 和 GEO 数据库的数据，我们研究了 DNAJC1 在 GBM 标本中的表达模式及其与临床特征的相关性。进行了功能丧失实验，以探讨 DNAJC1 对 GBM 细胞系的影响，通过共培养实验评估巨噬细胞浸润和功能标志物表达。

结果

我们的分析表明，在 GBM 中 DNAJC1 频繁过表达，与各种临床特征显著相关，包括 WHO 分级、IDH 状态、染色体 1p/19q 缺失和组织学类型。此外，Kaplan-Meier 和 ROC 分析显示 DNAJC1 是 GBM 患者的负预后预测因子和有前途的诊断生物标志物。功能研究表明，沉默 DNAJC1 可抑制细胞增殖和迁移，诱导细胞周期停滞，并增强细胞凋亡。机制上，DNAJC1 参与刺激细胞外基质重构，引发上皮-间充质转化（EMT）过程，并引发免疫抑制性巨噬细胞浸润。