Related Experiment Video
Updated: Jan 10, 2026
Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
USP54 Promotes Ferroptosis in Non-Small Cell Lung Cancer by Mediating FOXA2 Deubiquitination and Enhancing ACSL4
Rui-Shi Wei1, Yong-Ping Liu2, Chun-Dong Gu3
1Department of Thoracic Surgery, Changzhou Cancer Hospital, Changzhou, Jiangsu, China.
Abstract:
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, with a 5-year survival rate of less than 20% and a high risk of recurrence despite advances in treatment. This study aimed to identify new therapeutic targets to increase the effectiveness of NSCLC treatments. We examined the role of USP54 in ferroptosis using an MTT assay and assessed the levels of reactive oxygen species (ROS), ferrous iron (Fe2+), and malondialdehyde (MDA). To explore the underlying molecular mechanism, the intermolecular interactions was assessed using coimmunoprecipitation (Co-IP), chromatin immunoprecipitation (ChIP), and dual-luciferase reporter assays. We found that USP54 expression was reduced in NSCLC and that its overexpression inhibited NSCLC cell proliferation while inducing ferroptosis, as indicated by increased ROS, Fe2+, and MDA levels, along with changes in SLC7A11, GPX4, and ACSL4 expression. Additionally, USP54 mediated the deubiquitination of FOXA2, decreasing its degradation. And FOXA2 promoted ACSL4 transcription, which further induced ferroptosis in NSCLC cells. In conclusion, USP54 promotes ferroptosis and inhibits NSCLC progression by stabilizing FOXA2, which in turn activates ACSL4 transcription. This study provides a theoretical foundation for the development of therapies targeting USP54 or ACSL4 for NSCLC treatment.
Insights
Overexpressing USP54 inhibits non-small cell lung cancer (NSCLC) progression by promoting ferroptosis. USP54 stabilizes FOXA2, increasing ACSL4 transcription and inducing cell death in NSCLC.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Non-small cell lung cancer (NSCLC) has a poor prognosis, necessitating novel therapeutic strategies.
- Current treatments for NSCLC face challenges with recurrence and limited efficacy.
- Identifying new molecular targets is crucial for improving NSCLC treatment outcomes.
Purpose of the Study:
- To investigate the role of USP54 in ferroptosis as a potential therapeutic target for NSCLC.
- To elucidate the molecular mechanism by which USP54 influences NSCLC progression and cell death.
- To explore the relationship between USP54, FOXA2, and ACSL4 in the context of NSCLC.
Main Methods:
- MTT assays were used to assess cell proliferation.
- Levels of reactive oxygen species (ROS), ferrous iron (Fe2+), and malondialdehyde (MDA) were measured.
- Co-immunoprecipitation (Co-IP), chromatin immunoprecipitation (ChIP), and dual-luciferase reporter assays were employed to study molecular interactions and gene regulation.
Main Results:
- USP54 expression was found to be downregulated in NSCLC tissues.
- Overexpression of USP54 inhibited NSCLC cell proliferation and induced ferroptosis, evidenced by increased ROS, Fe2+, and MDA.
- USP54 stabilized FOXA2 by mediating its deubiquitination, leading to increased ACSL4 transcription and subsequent ferroptosis.
Conclusions:
- USP54 acts as a tumor suppressor in NSCLC by promoting ferroptosis.
- The USP54-FOXA2-ACSL4 axis represents a novel pathway regulating ferroptosis in NSCLC.
- Targeting USP54 or ACSL4 may offer a promising therapeutic approach for NSCLC treatment.
Related Concept Videos
01:16Necrosis
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
02:23Abnormal Proliferation