UBE2C promotes cell cycle progression and suppresses DNA damage-induced apoptosis in triple-negative breast cancer

IF 3.2 3区生物学 Q2 GENETICS & HEREDITY

DNA Repair Pub Date : 2025-10-01 Epub Date: 2025-10-09 DOI:10.1016/j.dnarep.2025.103901

Qin Hu , Kewu Wang , Chuanrong Chen , Jian Ding , Yang He , Zhaoning Ji

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引用次数: 0

Abstract

Background

Triple-negative breast cancer (TNBC), characterized by its aggressiveness, constitutes a unique breast cancer subtype, lacking effective targeted therapies. Its progression is often driven by cell cycle control dysfunction, impaired DNA damage handling, and resistance to apoptosis. Ubiquitin-conjugating enzyme E2C (UBE2C), an essential mitotic regulator, has been implicated in tumorigenesis and therapy resistance in several tumor types, but its relevance in TNBC is still poorly understood. This study focused on investigating the expression and functional importance of UBE2C in TNBC development.

Methods

UBE2C levels and their clinical relevance in TNBC were evaluated via transcriptomic data from TCGA and GTEx. Gene set enrichment analysis (GSEA) was performed to pinpoint UBE2C-associated biological pathways. Functional validation was conducted in MDA-MB-231 TNBC cell lines via qRT-PCR, Western blotting, flow cytometry, comet assay, and TUNEL staining to examine the effects of UBE2C modulation on cell cycle dynamics, DNA damage response, and apoptosis.

Results

UBE2C exhibited marked overexpression in TNBC tissues and cell lines relative to normal controls (P < 0.01), and its high expression was correlated with reduced overall survival (P = 0.01). GSEA indicated enrichment of cell cycle and DNA repair pathways in UBE2C-high samples, while apoptosis pathways were suppressed (FDR < 0.25). Functional assays demonstrated that UBE2C overexpression accelerated G1/S and G2/M transitions (P < 0.01), reduced DNA damage accumulation (P < 0.01), and suppressed apoptotic processes (P < 0.01), while UBE2C knockdown elicited the opposite effects.

Conclusion

UBE2C promotes TNBC cell survival through modulation of cell cycle progression, DNA repair mechanisms, and apoptosis signaling. These results suggested that UBE2C could be considered a promising biomarker and therapeutic target, particularly in combination with DNA-damaging agents for personalized TNBC therapy.

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UBE2C促进三阴性乳腺癌细胞周期进程，抑制DNA损伤诱导的细胞凋亡。

背景：三阴性乳腺癌（TNBC）具有侵袭性，是一种独特的乳腺癌亚型，缺乏有效的靶向治疗。其进展通常由细胞周期控制功能障碍、DNA损伤处理受损和细胞凋亡抵抗驱动。泛素偶联酶E2C （UBE2C）是一种重要的有丝分裂调节剂，与几种肿瘤类型的肿瘤发生和治疗耐药有关，但其在TNBC中的相关性仍然知之甚少。本研究的重点是探讨UBE2C在TNBC发展中的表达及其功能重要性。方法：通过TCGA和GTEx的转录组学数据评估TNBC中UBE2C水平及其临床相关性。通过基因集富集分析（GSEA）确定ube2c相关的生物学途径。通过qRT-PCR、Western blotting、流式细胞术、comet实验和TUNEL染色对MDA-MB-231 TNBC细胞株进行功能验证，研究UBE2C调控对细胞周期动力学、DNA损伤反应和凋亡的影响。结果：与正常对照相比，UBE2C在TNBC组织和细胞系中表现出明显的过表达(P 结论：UBE2C通过调节细胞周期进程、DNA修复机制和凋亡信号传导促进TNBC细胞存活。这些结果表明，UBE2C可以被认为是一个有前景的生物标志物和治疗靶点，特别是与dna损伤药物联合用于个性化TNBC治疗。

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

DNA Repair 生物-毒理学

CiteScore

7.60

自引率

5.30%

发文量

审稿时长

59 days

期刊介绍： DNA Repair provides a forum for the comprehensive coverage of DNA repair and cellular responses to DNA damage. The journal publishes original observations on genetic, cellular, biochemical, structural and molecular aspects of DNA repair, mutagenesis, cell cycle regulation, apoptosis and other biological responses in cells exposed to genomic insult, as well as their relationship to human disease. DNA Repair publishes full-length research articles, brief reports on research, and reviews. The journal welcomes articles describing databases, methods and new technologies supporting research on DNA repair and responses to DNA damage. Letters to the Editor, hot topics and classics in DNA repair, historical reflections, book reviews and meeting reports also will be considered for publication.