Potential role of SUMO-specific proteases 1 in ferroptosis

XIE Bin; BAI Meng; WU Yan; WO Lulu; HUANG Ying; ZHANG Jing

doi:10.3969/j.issn.1674-8115.2025.01.002

Shanghai Jiaotong Daxue xuebao. Yixue ban (Jan 2025)

Potential role of SUMO-specific proteases 1 in ferroptosis

XIE Bin,
BAI Meng,
WU Yan,
WO Lulu,
HUANG Ying,
ZHANG Jing

Affiliations

XIE Bin: 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
BAI Meng: 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
WU Yan: 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
WO Lulu: 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
HUANG Ying: 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: 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

DOI: https://doi.org/10.3969/j.issn.1674-8115.2025.01.002
Journal volume & issue: Vol. 45, no. 1
pp. 11 – 19

Abstract

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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.

Published in Shanghai Jiaotong Daxue xuebao. Yixue ban

ISSN: 1674-8115 (Print)
Publisher: Editorial Office of Journal of Shanghai Jiao Tong University (Medical Science)
Country of publisher: China
LCC subjects: Medicine
Website: https://xuebao.shsmu.edu.cn/EN/1674-8115/home.shtml

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