Scholarlink

Background <p>Endometrial cancer (EC) is a significant and serious gynecological cancer, constituting a considerable risk to women's health. The desumoylation of SUMO specific peptidase 5 (SENP5) is intricately linked with various cancers. Nonetheless, the function of SENP5 in EC and its regulation of EC progression through the related mechanism of desumoylation modification remain elusive.</p> Methods <p>Five samples of EC tumor tissues, along with para-cancerous tissues, were obtained. The expression of SENP5 in EC was assessed using reverse transcription–polymerase chain reaction (RT–qPCR), immunohistochemistry (IHC), and Western blot. HEC-1-B cells were treated with liposomes to interfere SENP5 and/or β-catenin expression. The methodologies employed to assess the impact of SENP5 on the proliferation of EC cells via β-catenin included RT–qPCR, Western blot, CCK8, EDU, and C11-BODIPY methods. Western blot, co-immunoprecipitation (CO-IP), and SUMOylation analysis were conducted to investigate the desumoylation modification of β-catenin by SENP5.</p> Results <p>SENP5 exhibited elevated expression levels in EC cancer tissues and was correlated with a negative prognosis for patients diagnosed with EC. The suppression of SENP5 inhibited the expression of β-catenin and GPX4, activated ferroptosis, and inhibited HEC-1-B&#xa0;-cell&#xa0;proliferation. Knockdown of β-catenin counteracted the impact of SENP5 overexpression on ferroptosis and HEC-1-B proliferation. In addition, SENP5 stabilized β-catenin level in HEC-1-B cells through desumoylation modification of the β-catenin protein.</p> Conclusions <p>SENP5 promotes GPX4-mediated ferroptosis resistance, thereby enhancing the proliferation of EC cells by regulating β-catenin desumoylation, this finding&#xa0;indicates that SENP5 may serve as a promising target for therapeutic interventions in the treatment of EC.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

SENP5 promotes endometrial cancer cell growth by regulating β-catenin deSUMOylation to enhance GPX4-resistance to ferroptosis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年5月24日

查看全文
  • Ziyuan Wang,
  • Yongmei Zhang,
  • Yongfang Zhang,
  • Qiuhong Deng,
  • Yandong Xi,
  • Wanxia He,
  • Xiaolong Ma

摘要

Background

Endometrial cancer (EC) is a significant and serious gynecological cancer, constituting a considerable risk to women's health. The desumoylation of SUMO specific peptidase 5 (SENP5) is intricately linked with various cancers. Nonetheless, the function of SENP5 in EC and its regulation of EC progression through the related mechanism of desumoylation modification remain elusive.

Methods

Five samples of EC tumor tissues, along with para-cancerous tissues, were obtained. The expression of SENP5 in EC was assessed using reverse transcription–polymerase chain reaction (RT–qPCR), immunohistochemistry (IHC), and Western blot. HEC-1-B cells were treated with liposomes to interfere SENP5 and/or β-catenin expression. The methodologies employed to assess the impact of SENP5 on the proliferation of EC cells via β-catenin included RT–qPCR, Western blot, CCK8, EDU, and C11-BODIPY methods. Western blot, co-immunoprecipitation (CO-IP), and SUMOylation analysis were conducted to investigate the desumoylation modification of β-catenin by SENP5.

Results

SENP5 exhibited elevated expression levels in EC cancer tissues and was correlated with a negative prognosis for patients diagnosed with EC. The suppression of SENP5 inhibited the expression of β-catenin and GPX4, activated ferroptosis, and inhibited HEC-1-B -cell proliferation. Knockdown of β-catenin counteracted the impact of SENP5 overexpression on ferroptosis and HEC-1-B proliferation. In addition, SENP5 stabilized β-catenin level in HEC-1-B cells through desumoylation modification of the β-catenin protein.

Conclusions

SENP5 promotes GPX4-mediated ferroptosis resistance, thereby enhancing the proliferation of EC cells by regulating β-catenin desumoylation, this finding indicates that SENP5 may serve as a promising target for therapeutic interventions in the treatment of EC.