Department of Pharmacy, Qilu Hospital of Shandong University, Jinan 250012, China.
National Glycoengineering Research Center, Shandong University, Qingdao 266237, China.
Exp Biol Med (Maywood). 2022 Sep;247(17):1529-1541. doi: 10.1177/15353702221099460. Epub 2022 Jun 20.
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 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.
作为中枢神经系统的一种重要肿瘤类型，神经胶质瘤的预后较差。三结构域蛋白 25（TRIM25）是一种重要的 E3 泛素连接酶，参与多种生物学过程。本研究旨在证明其在神经胶质瘤中的功能作用。从公共数据库（包括癌症基因组图谱（TCGA）、中国神经胶质瘤基因组图谱（CGGA）和分子脑肿瘤数据存储库（REMBRANDT））中获取数据。分析了 TRIM25 的表达模式及其与不同临床特征的关系。通过 Kaplan-Meier 分析比较不同 TRIM25 表达与神经胶质瘤患者生存的关系。随后，我们进行了生物信息学分析以研究 TRIM25 的生物学功能，并通过实验、CIBERSORT 算法和 ESTIMATE 评估进一步验证。TRIM25 在神经胶质瘤患者中表达上调，并可预测不良预后。生物信息学结果表明 TRIM25 参与凋亡和免疫调节。TRIM25 与神经胶质瘤中程序性死亡配体 1（PD-L1）相关和巨噬细胞诱导的免疫抑制有关。同时，沉默 TRIM25 促进神经胶质瘤细胞凋亡，这归因于其对 NF-κB 的调节。因此，TRIM25 通过 NF-κB 激活促进神经胶质瘤的恶性进展和抑制性免疫微环境，这可能在神经胶质瘤中发挥治疗作用。
