Evidence map›Paper›PMID 39206719›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024

FOXO1-NCOA4 Axis Contributes to Cisplatin-Induced Cochlea Spiral Ganglion Neuron Ferroptosis via Ferritinophagy.

Xue Wang, Lei Xu, Yu Meng, Fang Chen, Jinzhu Zhuang, Man Wang, Weibin An, Yuechen Han, Bo Chu, Renjie Chai and 2 more

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing 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

37 citing papers in PubMed.

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  8. Functionalized Biomimetic Scaffolds for Human-Derived Auditory Neural Circuit Construction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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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

12 authors.

Xue WangDepartment of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Jinan, 250022, China.ORCID 0009-0001-0621-2851
Lei XuDepartment of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Jinan, 250022, China.
Yu MengDepartment of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Jinan, 250022, China.
Fang ChenDepartment of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Jinan, 250022, China.
Jinzhu ZhuangDepartment of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Jinan, 250022, China.
Man WangDepartment of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Jinan, 250022, China.
Weibin AnDepartment of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Jinan, 250022, China.
Yuechen HanDepartment of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Jinan, 250022, China.
Bo ChuDepartment of Cell Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China.
Renjie ChaiState Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing, 210096, China.
Wenwen LiuDepartment of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Jinan, 250022, China.ORCID 0000-0001-6031-7972
Haibo WangDepartment of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Jinan, 250022, China.

Funding

2022 Open Project Fund of Guangdong Academy of Medical Sciences YKY-KF202201Major Fundamental Research Program of the Natural Science Foundation of Shandong Province ZR2020ZD39Major Fundamental Research Program of the Natural Science Foundation of Shandong Province ZR2021ZD40Major Program of National Natural Science Foundation of China 82196821National Key R&D Program of China 2020YFA0112503National Key R&D Program of China 2021YFA1101300National Key R&D Program of China 2021YFA1101800National Natural Science Foundation of China 82030029National Natural Science Foundation of China 82271172National Natural Science Foundation of China 82271176National Natural Science Foundation of China 82330033National Natural Science Foundation of China 92149304Natural Science Foundation of Jiangsu Province BK20232007Science and Technology Department of Sichuan Province 2021YFS0371Shenzhen Science and Technology Program JCYJ20190814093401920Shenzhen Science and Technology Program JCYJ20210324125608022Taishan Scholars Program of Shandong Province tsqn201909189
6 · The paper itself

Abstract

Mammalian cochlea spiral ganglion neurons (SGNs) are crucial for sound transmission, they can be damaged by chemotherapy drug cisplatin and lead to irreversible sensorineural hearing loss (SNHL), while such damage can also render cochlear implants ineffective. However, the mechanisms underlying cisplatin-induced SGNs damage and subsequent SNHL are still under debate and there is no currently effective clinical treatment. Here, this study demonstrates that ferroptosis is triggered in SGNs following exposure to cisplatin. Inhibiting ferroptosis protects against cisplatin-induced SGNs damage and hearing loss, while inducing ferroptosis intensifies these effects. Furthermore, cisplatin prompts nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy in SGNs, while knocking down NCOA4 mitigates cisplatin-induced ferroptosis and hearing loss. Notably, the upstream regulator of NCOA4 is identified and transcription factor forkhead box O1 (FOXO1) is shown to directly suppress NCOA4 expression in SGNs. The knocking down of FOXO1 amplifies NCOA4-mediated ferritinophagy, increases ferroptosis and lipid peroxidation, while disrupting the interaction between FOXO1 and NCOA4 in NCOA4 knock out mice prevents the cisplatin-induced SGN ferroptosis and hearing loss. Collectively, this study highlights the critical role of the FOXO1-NCOA4 axis in regulating ferritinophagy and ferroptosis in cisplatin-induced SGNs damage, offering promising therapeutic targets for SNHL mitigation.

Indexed as

CisplatinFerroptosisForkhead Box Protein O1Nuclear Receptor CoactivatorsSpiral GanglionAnimalsCochleaDisease Models, AnimalFerritinsHearing Loss, SensorineuralMiceMice, KnockoutNeuronsCisplatinFerritinsForkhead Box Protein O1Foxo1 protein, mouseNcoA4 protein, mouseNuclear Receptor Coactivatorscisplatinferritinophagyferroptosisforkhead box transcription factor O1hearing lossnuclear receptor coactivator 4spiral ganglion neuron

Identifiers

PMID39206719
PMCPMC11515924

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Registered trials

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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.