OTUB1 promotes glioma progression by stabilizing TRAF4

IF 4.4 2区生物学 Q2 CELL BIOLOGY

Cellular signalling Pub Date : 2025-03-14 DOI:10.1016/j.cellsig.2025.111704

Hongjun Liu , Shasha Tan , Zhou Li , Jian Qi , Xiaoping Tang , Junhao Zhang

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引用次数: 0

Abstract

Background

Glioma is a highly heterogeneous brain tumor with poor prognosis. This study aims to investigate the functional role of OTUB1 in glioma and its impact on TRAF4 stability, seeking potential therapeutic targets.

Methods

We mined single-cell sequencing data from 12 glioma patients to analyze the heterogeneity of 20,145 glioma cells. The expression of OTUB1 in glioma tissues and cell lines was assessed using Western blot and qPCR. Additionally, immunoprecipitation and ubiquitination assays were conducted to evaluate the effect of OTUB1 on TRAF4 and its role in regulating TRAF4 stability. In vitro assays were performed to assess the effects of OTUB1 on cell proliferation, migration, and clonogenicity, while in vivo experiments using xenograft models in nude mice validated the impact of OTUB1 on tumor growth.

Results

OTUB1 was found to be significantly overexpressed in glioma tissues, correlating with poor patient outcomes. Knockdown of OTUB1 markedly inhibited the proliferation and migration of LN229 and U87MG cells while increasing apoptosis. Immunoprecipitation studies revealed that OTUB1 stabilizes TRAF4 by inhibiting its ubiquitination, thereby promoting glioma cell proliferation and invasion. In vivo, tumors with OTUB1 knockdown demonstrated significantly reduced growth rates.

Conclusion

OTUB1 plays a critical role in glioma progression and may serve as a novel therapeutic target. The development of inhibitors targeting OTUB1 could potentially improve outcomes for glioma patients.

查看原文本刊更多论文

OTUB1通过稳定TRAF4促进胶质瘤进展。

背景：胶质瘤是一种高度异质性的脑肿瘤，预后较差。本研究旨在探讨OTUB1在胶质瘤中的功能作用及其对TRAF4稳定性的影响，寻找潜在的治疗靶点。方法：我们挖掘了12例胶质瘤患者的单细胞测序数据，分析了20145个胶质瘤细胞的异质性。采用Western blot和qPCR检测胶质瘤组织和细胞系中OTUB1的表达。此外，通过免疫沉淀和泛素化实验来评估OTUB1对TRAF4的影响及其在调节TRAF4稳定性中的作用。体外实验评估了OTUB1对细胞增殖、迁移和克隆原性的影响，体内实验利用裸鼠异种移植模型验证了OTUB1对肿瘤生长的影响。结果：OTUB1在胶质瘤组织中显著过表达，与患者预后不良相关。敲低OTUB1可显著抑制LN229和U87MG细胞的增殖和迁移，同时增加凋亡。免疫沉淀研究发现OTUB1通过抑制TRAF4的泛素化来稳定TRAF4，从而促进胶质瘤细胞的增殖和侵袭。在体内，OTUB1基因敲低的肿瘤生长速度显著降低。结论：OTUB1在胶质瘤的进展中起关键作用，可能成为新的治疗靶点。针对OTUB1的抑制剂的开发可能潜在地改善胶质瘤患者的预后。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cellular signalling 生物-细胞生物学

CiteScore

8.40

自引率

0.00%

发文量

250

审稿时长

27 days

期刊介绍： Cellular Signalling publishes original research describing fundamental and clinical findings on the mechanisms, actions and structural components of cellular signalling systems in vitro and in vivo. Cellular Signalling aims at full length research papers defining signalling systems ranging from microorganisms to cells, tissues and higher organisms.