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Background <p>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.</p> Methods <p>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.</p> Results <p>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.</p> Conclusion <p>Our research identifies the SENP5/CDK1 axis as a key player in BRCA progression, highlighting its potential as a therapeutic target.</p>

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SENP5 drives breast cancer progression through deSUMOYlation of CDK1

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月5日

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

摘要

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.