NDLI: USP2 reversed cisplatin resistance through p53-mediated ferroptosis in NSCLC

Content Provider	Springer Nature : BioMed Central
Author	Gong, Yanmei Li, Ruichao Zhang, Rui Jia, Li
Abstract	Background It has demonstrated the indispensable role of ferroptosis in conferring cisplatin resistance in non-small cell lung cancer (NSCLC), as well as the involvement of ubiquitin-specific protease (USP) in regulating ferroptosis. This paper aspired to the mechanism of USP2 and ferroptosis on NSCLC cisplatin resistance. Methods Ubiquitin-specific protease mRNA expression, was detected through RT-qPCR. In vitro functional assays assessed the effects of USP2 overexpression on DDP resistance, cell proliferation capability, and ferroptosis markers in A549/DDP and H1299/DDP cells. Ubiquitination assays evaluated the ubiquitination levels of p53 following USP2 overexpression. Co-immunoprecipitation (Co-IP) assays confirmed the binding relationship between USP2 and p53. In vivo experiments in mice explored the specific role of the USP2-p53 axis in a xenograft tumor model. Results USP2 expression was suppressed in cisplatin-resistant NSCLC cells. USP2 overexpression inhibited cell viability in cisplatin-resistant cells. Among the ferroptosis markers, the results showed that USP2 overexpression promoted LDH release, Fe2+ level, MDA and Lipid ROS, while inhibited GPX4 activity and GSH levels. The WB results revealed that USP2 overexpression inhibited GPX4, SLC7A11 and cytoplasm p53 protein expression, while promoted the nucleus p53 protein expression. Moreover, USP2 directly bound to p53 and USP2 overexpression stabilized p53 protein by suppressing its ubiquitination. In vivo experiments further suggest that the USP2-p53 pathway plays a crucial role in regulating cisplatin sensitivity in A549/DDP cells. Conclusion USP2 acted on the K305R site of p53, which resulted in its deubiquitination. This cellular process could modulate cisplatin resistance through ferroptosis in NSCLC. This study could provide a potential therapeutic target to NSCLC.
Related Links	https://bmcmedgenomics.biomedcentral.com/counter/pdf/10.1186/s12920-025-02108-5.pdf
Ending Page	13
Page Count	13
Starting Page	1
File Format	HTM / HTML
ISSN	17558794
DOI	10.1186/s12920-025-02108-5
Journal	BMC Medical Genomics
Issue Number	1
Volume Number	18
Language	English
Publisher	BioMed Central
Publisher Date	2025-02-26
Access Restriction	Open
Subject Keyword	Human Genetics Microarrays Gene Expression USP2 p53 Cisplatin resistance Ferroptosis
Content Type	Text
Resource Type	Article
Subject	Genetics (clinical) Genetics
Journal Impact Factor	2.1/2023
5-Year Journal Impact Factor	2.5/2023

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Ferroptosis related gene signature in T cell-mediated rejection after kidney transplantation

Bioinformatics analysis of ferroptosis in frozen shoulder

Identification of the ferroptosis-related long non-coding RNAs signature to improve the prognosis prediction and immunotherapy response in patients with NSCLC

Delineation and authentication of ferroptosis genes in ventilator-induced lung injury

The identification of a two-gene prognostic model based on cisplatin resistance-related ceRNA network in small cell lung cancer

Comprehensive analysis of ferroptosis-related genes and prognosis of cutaneous melanoma

Identification of ferroptosis related biomarkers and immune infiltration in Parkinson’s disease by integrated bioinformatic analysis

High-throughput sequencing reveals Jatrorrhizine inhibits colorectal cancer growth by ferroptosis-related genes

Inhibition of SMYD2 Sensitized Cisplatin to Resistant Cells in NSCLC Through Activating p53 Pathway

USP2 reversed cisplatin resistance through p53-mediated ferroptosis in NSCLC

Similar Documents

Ferroptosis related gene signature in T cell-mediated rejection after kidney transplantation

Bioinformatics analysis of ferroptosis in frozen shoulder

Identification of the ferroptosis-related long non-coding RNAs signature to improve the prognosis prediction and immunotherapy response in patients with NSCLC

Delineation and authentication of ferroptosis genes in ventilator-induced lung injury

The identification of a two-gene prognostic model based on cisplatin resistance-related ceRNA network in small cell lung cancer

Comprehensive analysis of ferroptosis-related genes and prognosis of cutaneous melanoma

Identification of ferroptosis related biomarkers and immune infiltration in Parkinson’s disease by integrated bioinformatic analysis

High-throughput sequencing reveals Jatrorrhizine inhibits colorectal cancer growth by ferroptosis-related genes

Inhibition of SMYD2 Sensitized Cisplatin to Resistant Cells in NSCLC Through Activating p53 Pathway

USP2 reversed cisplatin resistance through p53-mediated ferroptosis in NSCLC