Evidence map›Paper›PMID 41422226›Full record

ArticleCell death & disease2025

Suppressing the OTUD7A/KDM5B/GABPA axis enhances the sensitivity of cisplatin through inducing ferroptosis in KRAS-mutant LUAD.

Rujia Si, Ziyang Shen, Ying Sui, Yue Shi, Yihan Zhang, Bowen Hu, Xin Chen, Bing Feng, Miao Lin Zhu, Xiaofeng Sha and 5 more

Abstract read
In one paragraph

Article in Cell death & disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Rujia Si *Department of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China.
Ziyang Shen *Department of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China.ORCID http://orcid.org/0000-0002-6923-8338
Ying Sui *Department of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China.ORCID http://orcid.org/0009-0007-8681-6519
Yue ShiDepartment of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China.
Yihan ZhangDepartment of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China.
Bowen HuDepartment of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China.
Xin ChenDepartment of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China.
Bing FengDepartment of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China.
Miao Lin ZhuDepartment of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China.
Xiaofeng ShaDepartment of Medical Oncology, Hongze District People's Hospital of Huai'an City, Huai'an, Jiangsu Province, China.
Ning DingWuxi Huishan District People's Hospital, Wuxi, China.
Guoren ZhouDepartment of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China.
Feng JiangDepartment of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China.ORCID http://orcid.org/0000-0001-6569-5956
Cong XuDepartment of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China.
Bo ShenDepartment of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China. shenbo987@njmu.edu.cn.ORCID http://orcid.org/0000-0002-8782-3151

Funding

Nanjing Medical University (NMU) 2024KF0228National Natural Science Foundation of China (National Science Foundation of China) 82272863
6 · The paper itself

Abstract

KRAS-mutant lung adenocarcinoma (LUAD), due to its evolution of more complex antioxidant metabolic mechanisms, exhibits poorer sensitivity to conventional platinum-based drugs compared to other types of LUAD. Ferroptosis, as a means of inducing cell death in cancer therapy, shows unique features and potential therapeutic effects compared to the conventional form of apoptosis, which is frequently obstructed by drug resistance. In human KRAS-mutant LUAD cell lines and mouse models, we found that the deubiquitinase OTU deubiquitinase 7A (OTUD7A) precisely regulates the lysine demethylase 5B (KDM5B). Inhibition of KDM5B expression increases the H4K20me3 level, which in turn downregulates the expression of transcription factor GABPA associated with mitochondrial function, ultimately promoting the production of more Reactive Oxygen Species (ROS) by mitochondria and inducing ferroptosis. Additionally, in in vivo organoid models, cisplatin (CDDP) induced ferroptosis combined with GABPA inhibition demonstrated superior anticancer effects compared to conventional platinum-based drugs. This research identifies new targets and regulatory networks that hold promise for developing ferroptosis-based therapies for KRAS-mutant LUAD.

Indexed as

Adenocarcinoma of LungCisplatinFerroptosisGA-Binding Protein Transcription FactorLung NeoplasmsProto-Oncogene Proteins p21(ras)AnimalsAntineoplastic AgentsCell Line, TumorHumansMiceMice, NudeMitochondriaMutationReactive Oxygen SpeciesAntineoplastic AgentsCisplatinGA-Binding Protein Transcription FactorKRAS protein, humanProto-Oncogene Proteins p21(ras)Reactive Oxygen Species

Identifiers

PMID41422226
PMCPMC12848020

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.