SENP5 drives breast cancer progression through deSUMOYlation of CDK1.

IF 5.6 1区医学 Q1 Medicine

Breast Cancer Research Pub Date : 2025-06-05 DOI:10.1186/s13058-025-02054-1

Cui Chen, Hanming Yao, Haiqing Jie, Zhenkang Liang, Yuxuan Zhang, Xinyun Wen, Jinze Zhao, Huiping Xiong, Zongheng Zheng, Juekun Wu

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引用次数: 0

Abstract

Background: Breast cancer (BRCA) remains a significant global health concern, with the need for novel therapeutic targets to improve patient outcomes. The role of the SENP family of de-SUMOylating enzymes in BRCA is not yet fully understood.

Methods: The expression and prognostic value of SENP family in BRCA were analyzed using the TCGA database. GSEA was conducted to identify correlations between SENP5 expression and cell cycle pathways. Experiments including Western blotting, RT-qPCR, CCK8 assays, colony formation assays, EdU staining, wound healing assays, and transwell assays were used to assess the impact of SENP5 knockdown on BRCA cell proliferation, migration, and invasion. Co-immunoprecipitation and fluorescence co-localization studies were employed to investigate the interaction between SENP5 and CDK1. The effects of combining SENP5 knockdown with CDK1 inhibition were evaluated in MDA-MB-231 xenograft mouse model.

Results: SENP5 was found to be overexpressed in BRCA and associated with poor prognosis. Knockdown of SENP5 significantly inhibited BRCA cell proliferation and migration. GSEA revealed a strong correlation between SENP5 and the cell cycle, particularly the G2M checkpoint and E2F target pathways. SENP5 was shown to promote cell cycle progression by upregulating CDK1. Mechanistically, SENP5 mediates the de-SUMOylation of CDK1, reducing its degradation via the ubiquitin-proteasome pathway and increasing CDK1 expression. In vivo, the combination of SENP5 knockdown and CDK1 inhibition significantly suppressed BRCA tumor growth.

Conclusion: Our research identifies the SENP5/CDK1 axis as a key player in BRCA progression, highlighting its potential as a therapeutic target.

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SENP5通过CDK1的deSUMOYlation驱动乳腺癌进展。

背景：乳腺癌（BRCA）仍然是一个重要的全球健康问题，需要新的治疗靶点来改善患者的预后。去summoylating酶SENP家族在BRCA中的作用尚不完全清楚。方法：应用TCGA数据库分析SENP家族在BRCA中的表达及预后价值。通过GSEA鉴定SENP5表达与细胞周期通路之间的相关性。通过Western blotting、RT-qPCR、CCK8检测、菌落形成检测、EdU染色、伤口愈合检测和transwell检测来评估SENP5敲低对BRCA细胞增殖、迁移和侵袭的影响。采用共免疫沉淀和荧光共定位研究SENP5和CDK1之间的相互作用。在MDA-MB-231异种移植小鼠模型中评估了SENP5敲除与CDK1抑制联合作用的效果。结果：SENP5在BRCA中过表达，与预后不良相关。SENP5基因敲低可显著抑制BRCA细胞的增殖和迁移。GSEA揭示了SENP5与细胞周期，特别是G2M检查点和E2F靶点通路之间的强相关性。SENP5被证明通过上调CDK1促进细胞周期进程。机制上，SENP5介导CDK1的去sumo化，通过泛素-蛋白酶体途径减少其降解，增加CDK1表达。在体内，SENP5敲低和CDK1抑制联合显著抑制BRCA肿瘤生长。结论：我们的研究确定了SENP5/CDK1轴在BRCA进展中起关键作用，突出了其作为治疗靶点的潜力。

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

Breast Cancer Research ONCOLOGY-

CiteScore

12.00

自引率

0.00%

发文量

审稿时长

12 weeks

期刊介绍： Breast Cancer Research, an international, peer-reviewed online journal, publishes original research, reviews, editorials, and reports. It features open-access research articles of exceptional interest across all areas of biology and medicine relevant to breast cancer. This includes normal mammary gland biology, with a special emphasis on the genetic, biochemical, and cellular basis of breast cancer. In addition to basic research, the journal covers preclinical, translational, and clinical studies with a biological basis, including Phase I and Phase II trials.