TIFA enhances glycolysis through E2F1 and promotes the progression of glioma

IF 4.4 2区 生物学 Q2 CELL BIOLOGY Cellular signalling Pub Date : 2024-10-29 DOI:10.1016/j.cellsig.2024.111498
Zhibing Liu , Miaolong He , Zeshun Yu , Longbo Ma , Xiuwen Wang , Fangling Ning
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Abstract

Objective

TRAF interacting protein with forkhead associated domain (TIFA) influence progression of many cancers. However, its role in glioma remains to be explored. This study investigated the function of TIFA in glioma.

Methods

The TIFA expression in glioma and patient outcomes were analyzed using online database. Gene set enrichment analysis (GSEA) revealed related mechanisms of TIFA in glioma. TIFA's effects on glioma glycolysis and growth were assessed using in vitro and in vivo experiments. Moreover, luciferase reporter and ChIP were employed to explore the interactions among E2F1, GLUT1, HK2, and LDHA. The subcutaneous xenograft assay further elaborated the effects of TIFA in glioma.

Results

We found overexpressed TIFA in glioma. Moreover, the high TIFA expression was associated with poor prognosis of glioma. Furthermore, GSEA indicated that overexpressed TIFA promoted E2F1 and glycolysis. Knockdown of TIFA decreased glioma development in cell and mice. TIFA knockdown down-regulated the expression of E2F1, GLUT1, HK2, and LDHA.

Conclusions

The study provides evidence that TIFA regulates E2F1 expression in glioma cells and promotes the proliferation, migration, and glycolysis. TIFA might be an advantageous therapeutic strategy against glioma.

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TIFA 通过 E2F1 增强糖酵解,促进胶质瘤的进展。
目的具有叉头相关结构域的 TRAF 互作蛋白(TIFA)会影响多种癌症的进展。然而,它在胶质瘤中的作用仍有待探索。本研究探讨了TIFA在胶质瘤中的功能:方法:利用在线数据库分析 TIFA 在胶质瘤中的表达及患者预后。基因组富集分析(GSEA)揭示了TIFA在胶质瘤中的相关机制。通过体外和体内实验评估了TIFA对胶质瘤糖酵解和生长的影响。此外,还采用荧光素酶报告和ChIP技术探讨了E2F1、GLUT1、HK2和LDHA之间的相互作用。皮下异种移植实验进一步阐述了TIFA在胶质瘤中的作用:结果:我们发现TIFA在胶质瘤中过表达。此外,TIFA的高表达与胶质瘤的不良预后有关。此外,GSEA表明过表达的TIFA促进了E2F1和糖酵解。敲除 TIFA 可减少胶质瘤在细胞和小鼠中的发展。TIFA敲除可下调E2F1、GLUT1、HK2和LDHA的表达:该研究提供了证据,证明 TIFA 可调节胶质瘤细胞中 E2F1 的表达,并促进细胞的增殖、迁移和糖酵解。TIFA可能是一种治疗胶质瘤的有利策略。
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来源期刊
Cellular signalling
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.
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