USP30 Aggravating the Malignant Progression of Breast Cancer and Its Resistance to Tamoxifen by Inhibiting the Ubiquitination of TOMM40

IF 3.2 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-04-14 DOI:10.1002/jbt.70258

Xinran Gao, Junbiao Liu, Baoqing Jia, Jiaxin Guo

{"title":"USP30 Aggravating the Malignant Progression of Breast Cancer and Its Resistance to Tamoxifen by Inhibiting the Ubiquitination of TOMM40","authors":"Xinran Gao, Junbiao Liu, Baoqing Jia, Jiaxin Guo","doi":"10.1002/jbt.70258","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n <p>Breast cancer (BC) is the most common malignancy among women, with high incidence and mortality rates globally. Translocase of outer mitochondrial membrane 40 (TOMM40) has also been identified as an important prognostic biomarker for BC. Meanwhile, the ubiquitin-specific protease 30 (USP30) has also been shown to promote BC progression. However, the specific mechanisms underlying the role of USP30/TOMM40 in BC development remain unclear. Therefore, this study aims to delve into the potential mechanisms of USP30/TOMM40 in the progression of BC. The expression of TOMM40 and USP30 in BC tumors and cells was verified by bioinformatics analysis and western blot (WB). The effects of USP30/TOMM40 on BC cell proliferation, angiogenesis, glycolysis, and ferroptosis were determined by colony formation, tube formation assays and commercial kits. The co-immunoprecipitation (Co-IP) experiment was applied to verify the interaction between USP30 and TOMM40. The ubiquitination level of TOMM40 was detected by ubiquitinated antibodies. The effect of tamoxifen (TAM) on BC cell viability was measured by MTT assay. TOMM40 and USP30 were highly expressed in BC tumors and cells. Silencing TOMM40 blocked the proliferation, angiogenesis, glycolytic, and induced ferroptosis of BC cells. USP30 bound to TOMM40 and reduced its ubiquitination level. TOMM40 overexpressed abolished the tumor suppressive effect of USP30 knockdown and enhanced the resistance of BC to TAM. In conclusion, USP30 deubiquitinating TOMM40 promoted BC development and TAM resistance.</p>\n </section>\n </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 4","pages":""},"PeriodicalIF":3.2000,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Biochemical and Molecular Toxicology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jbt.70258","RegionNum":3,"RegionCategory":"医学","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

Breast cancer (BC) is the most common malignancy among women, with high incidence and mortality rates globally. Translocase of outer mitochondrial membrane 40 (TOMM40) has also been identified as an important prognostic biomarker for BC. Meanwhile, the ubiquitin-specific protease 30 (USP30) has also been shown to promote BC progression. However, the specific mechanisms underlying the role of USP30/TOMM40 in BC development remain unclear. Therefore, this study aims to delve into the potential mechanisms of USP30/TOMM40 in the progression of BC. The expression of TOMM40 and USP30 in BC tumors and cells was verified by bioinformatics analysis and western blot (WB). The effects of USP30/TOMM40 on BC cell proliferation, angiogenesis, glycolysis, and ferroptosis were determined by colony formation, tube formation assays and commercial kits. The co-immunoprecipitation (Co-IP) experiment was applied to verify the interaction between USP30 and TOMM40. The ubiquitination level of TOMM40 was detected by ubiquitinated antibodies. The effect of tamoxifen (TAM) on BC cell viability was measured by MTT assay. TOMM40 and USP30 were highly expressed in BC tumors and cells. Silencing TOMM40 blocked the proliferation, angiogenesis, glycolytic, and induced ferroptosis of BC cells. USP30 bound to TOMM40 and reduced its ubiquitination level. TOMM40 overexpressed abolished the tumor suppressive effect of USP30 knockdown and enhanced the resistance of BC to TAM. In conclusion, USP30 deubiquitinating TOMM40 promoted BC development and TAM resistance.

Abstract Image

查看原文本刊更多论文

USP30通过抑制TOMM40泛素化加速乳腺癌恶性进展及其对他莫昔芬的耐药性

乳腺癌（BC）是妇女中最常见的恶性肿瘤，在全球范围内发病率和死亡率都很高。外线粒体膜转位酶40 （TOMM40）也被认为是BC的重要预后生物标志物。同时，泛素特异性蛋白酶30 （USP30）也被证明可以促进BC的进展。然而，USP30/TOMM40在BC发展中作用的具体机制尚不清楚。因此，本研究旨在探讨USP30/TOMM40在BC进展中的潜在机制。通过生物信息学分析和western blot （WB）验证TOMM40和USP30在BC肿瘤和细胞中的表达。USP30/TOMM40对BC细胞增殖、血管生成、糖酵解和铁凋亡的影响通过集落形成、管形成试验和商业试剂盒进行检测。采用共免疫沉淀（Co-IP）实验验证USP30与TOMM40之间的相互作用。通过泛素化抗体检测TOMM40的泛素化水平。采用MTT法检测他莫昔芬（TAM）对BC细胞活力的影响。TOMM40和USP30在BC肿瘤和细胞中高表达。沉默TOMM40可阻断BC细胞的增殖、血管生成、糖酵解并诱导铁下垂。USP30与TOMM40结合并降低其泛素化水平。TOMM40过表达消除了USP30敲低的抑瘤作用，增强了BC对TAM的抵抗。综上所述，USP30去泛素化TOMM40促进了BC的发展和TAM的耐药性。

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

Journal of Biochemical and Molecular Toxicology 生物-毒理学

CiteScore

5.80

自引率

2.80%

发文量

277

审稿时长

6-12 weeks

期刊介绍： The Journal of Biochemical and Molecular Toxicology is an international journal that contains original research papers, rapid communications, mini-reviews, and book reviews, all focusing on the molecular mechanisms of action and detoxication of exogenous and endogenous chemicals and toxic agents. The scope includes effects on the organism at all stages of development, on organ systems, tissues, and cells as well as on enzymes, receptors, hormones, and genes. The biochemical and molecular aspects of uptake, transport, storage, excretion, lactivation and detoxication of drugs, agricultural, industrial and environmental chemicals, natural products and food additives are all subjects suitable for publication. Of particular interest are aspects of molecular biology related to biochemical toxicology. These include studies of the expression of genes related to detoxication and activation enzymes, toxicants with modes of action involving effects on nucleic acids, gene expression and protein synthesis, and the toxicity of products derived from biotechnology.