Journal of Shanghai Jiao Tong University (Medical Science) >

2025 , Vol. 45 >Issue 1: 11 - 19

DOI: https://doi.org/10.3969/j.issn.1674-8115.2025.01.002

Basic research

Potential role of SUMO-specific proteases 1 in ferroptosis

  • XIE Bin ,
  • BAI Meng ,
  • WU Yan ,
  • WO Lulu ,
  • HUANG Ying ,
  • ZHANG Jing
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  • Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University College of Basic Medical Sciences, Shanghai 200025, China
ZHANG Jing, E-mail: jingzhang@shsmu.edu.cn.

Received date: 2024-01-30

  Accepted date: 2024-08-20

  Online published: 2025-01-28

Supported by

Innovative Research Team of High-Level Local Universities in Shanghai(SHSMU-ZDCX20212000)

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Abstract

Objective ·To explore the potential role of SUMO-specific protease 1 (SENP1) in ferroptosis. Methods ·The Cancer Genome Atlas (TCGA) database was used to analyze the correlation between the expression levels of SENP1 and the ferroptosis-related genes, acyl-CoA synthetase long chain family member 4 (ACSL4) and glutathione peroxidase 4 (GPX4). Ferroptosis in human fibrosarcoma HT1080 cells, murine fibrosarcoma MCA-205 cells, and human embryonic kidney 293T cells was induced by RAS-selective lethal 3 (RSL3). Quantitative real-time PCR (RT-qPCR) and Western blotting were used to detect the expression of SENP1. In 293T cells, immunoprecipitation-mass spectrometry was used to investigate the interacting proteins of SENP1 in the process of ferroptosis. The Flag-SENP1 plasmid was transiently transfected into 293T cells, and the overexpression efficiency of SENP1, along with the expression levels of ferroptosis-related genes ACSL4 and GPX4,was assessed by RT-qPCR and Western blotting. Results ·TCGA database analysis showed that the expression of SENP1 was positively correlated with ACSL4 and negatively correlated with GPX4 in most tumor tissues. RT-qPCR and Western blotting showed that the expression level of SENP1 was significantly down-regulated in RSL3-treated HT1080, MCA-205, and 293T cells. Immunoprecipitation-mass spectrometry showed that SENP1 enriched SUMO molecules in the process of ferroptosis. Western blotting showed that the level of ACSL4 protein increased after SENP1 overexpression, and there was no significant change in the level of GPX4 protein. RT-qPCR showed that after SENP1 overexpression, there was no significant change in the mRNA levels of ACSL4 and GPX4. Conclusion ·SENP1 gene expression is downregulated during ferroptosis, and may regulate the stability of ferroptosis-related protein ACSL4.

Key words： ferroptosis; SUMO-specific protease 1 (SENP1); acyl-CoA synthetase long chain family member 4 (ACSL4); glutathione peroxidase 4 (GPX4); small ubiquitin-related modifier protein (SUMO)

Cite this article

XIE Bin , BAI Meng , WU Yan , WO Lulu , HUANG Ying , ZHANG Jing . Potential role of SUMO-specific proteases 1 in ferroptosis[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025 , 45(1) : 11 -19 . DOI: 10.3969/j.issn.1674-8115.2025.01.002

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