Work

USP54 Promotes Ferroptosis in Non‐Small Cell Lung Cancer by Mediating FOXA2 Deubiquitination and Enhancing ACSL4 Transcription

Year: 2025

Type: article

Abstract: 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 (Fe 2+ ), 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, Fe 2+ , 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.

Source: The Kaohsiung Journal of Medical Sciences

DOI: 10.1002/kjm2.70139

Authors: Rui‐Shi Wei, Yong‐Ping Liu, Chun‐Dong Gu, Shi‐Lei Zhao, Li Feng, Jian‐Rong Yu

Institutions: Dalian Medical University, First Affiliated Hospital of Dalian Medical University

Language: English

Topic: Ferroptosis and cancer prognosis

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,200