TRIM34 inhibits triple-negative breast cancer progression by attenuating fatty acid synthesis via facilitating FASN ubiquitination

IF 4.2 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-06-19 DOI:10.1016/j.bbadis.2025.167958

Yong Li , Jijun Shan , Shanqing Liu , Yan Shen , Lianjie Niu , Qixin Mao , Xiaobing Chen

{"title":"TRIM34 inhibits triple-negative breast cancer progression by attenuating fatty acid synthesis via facilitating FASN ubiquitination","authors":"Yong Li , Jijun Shan , Shanqing Liu , Yan Shen , Lianjie Niu , Qixin Mao , Xiaobing Chen","doi":"10.1016/j.bbadis.2025.167958","DOIUrl":null,"url":null,"abstract":"<div><div>TRIM34, an E3 ubiquitin ligase, plays a pivotal role in regulating protein degradation, the cell cycle, and tumor progression. So far, the precise mechanisms and function of TRIM34 in triple-negative breast cancer (TNBC) remain unclear. In this study, we investigated the effect of TRIM34 in TNBC through in vitro and in vivo experiments. We identified TRIM34 as a significant regulator of Fatty Acid Synthase (FASN). TRIM34 was found to be downregulated in TNBC tissues, and its overexpression inhibited cell proliferation and migration by reducing fatty acid synthesis. Mechanistically, TRIM34 directly interacts with FASN, promoting its K48-linked ubiquitination and degradation. Clinical analysis revealed a negative correlation between TRIM34 and FASN expression, and low TRIM34 levels associated with poor patient prognosis. TRIM34 is a tumor suppressor and impedes TNBC progression by targeting FASN, offering a promising avenue for therapeutic intervention.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 7","pages":"Article 167958"},"PeriodicalIF":4.2000,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochimica et biophysica acta. Molecular basis of disease","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0925443925003060","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

TRIM34, an E3 ubiquitin ligase, plays a pivotal role in regulating protein degradation, the cell cycle, and tumor progression. So far, the precise mechanisms and function of TRIM34 in triple-negative breast cancer (TNBC) remain unclear. In this study, we investigated the effect of TRIM34 in TNBC through in vitro and in vivo experiments. We identified TRIM34 as a significant regulator of Fatty Acid Synthase (FASN). TRIM34 was found to be downregulated in TNBC tissues, and its overexpression inhibited cell proliferation and migration by reducing fatty acid synthesis. Mechanistically, TRIM34 directly interacts with FASN, promoting its K48-linked ubiquitination and degradation. Clinical analysis revealed a negative correlation between TRIM34 and FASN expression, and low TRIM34 levels associated with poor patient prognosis. TRIM34 is a tumor suppressor and impedes TNBC progression by targeting FASN, offering a promising avenue for therapeutic intervention.

Abstract Image

查看原文本刊更多论文

TRIM34通过促进FASN泛素化来抑制脂肪酸合成，从而抑制三阴性乳腺癌的进展

TRIM34是一种E3泛素连接酶，在调节蛋白质降解、细胞周期和肿瘤进展中起关键作用。迄今为止，TRIM34在三阴性乳腺癌（TNBC）中的确切机制和功能尚不清楚。在本研究中，我们通过体外和体内实验研究了TRIM34在TNBC中的作用。我们发现TRIM34是脂肪酸合成酶（FASN）的重要调节因子。TRIM34在TNBC组织中下调，其过表达通过减少脂肪酸合成抑制细胞增殖和迁移。机制上，TRIM34直接与FASN相互作用，促进其与k48相关的泛素化和降解。临床分析显示TRIM34与FASN表达呈负相关，TRIM34水平低与患者预后差相关。TRIM34是一种肿瘤抑制因子，通过靶向FASN阻止TNBC进展，为治疗干预提供了一条有希望的途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Biochimica et biophysica acta. Molecular basis of disease 生物-生化与分子生物学

CiteScore

12.30

自引率

0.00%

发文量

218

审稿时长

32 days

期刊介绍： BBA Molecular Basis of Disease addresses the biochemistry and molecular genetics of disease processes and models of human disease. This journal covers aspects of aging, cancer, metabolic-, neurological-, and immunological-based disease. Manuscripts focused on using animal models to elucidate biochemical and mechanistic insight in each of these conditions, are particularly encouraged. Manuscripts should emphasize the underlying mechanisms of disease pathways and provide novel contributions to the understanding and/or treatment of these disorders. Highly descriptive and method development submissions may be declined without full review. The submission of uninvited reviews to BBA - Molecular Basis of Disease is strongly discouraged, and any such uninvited review should be accompanied by a coverletter outlining the compelling reasons why the review should be considered.