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Regulation of lipid droplets accumulation by the Hippo–YAP/COX2 signaling pathway in neomycin-induced ototoxicity
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  • Published: 16 April 2026

Regulation of lipid droplets accumulation by the Hippo–YAP/COX2 signaling pathway in neomycin-induced ototoxicity

  • Wenli Hao1 na1,
  • Song Gao1 na1,
  • Suhan Guo1,
  • Jingjing Luo1,
  • Siyu Li1,
  • Junze Lu1,
  • Lulu Jiang2,
  • Jie Lu3,
  • Nan Wang1,
  • Aijia Ran1,
  • Xiaoyun Qian1,4,
  • Xia Gao  ORCID: orcid.org/0000-0002-4539-59291,4,
  • Chenjie Yu  ORCID: orcid.org/0000-0002-6734-62471,4 &
  • …
  • Cheng Cheng  ORCID: orcid.org/0009-0003-3592-90471,4,5 

Cell Death Discovery , Article number:  (2026) Cite this article

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Gene regulation
  • Lipid signalling

Abstract

Lipid metabolism is an important biological process that maintains the dynamic balance of several key functions, such as intracellular energy metabolism, signal transduction, and membrane remodeling. However, the role of lipid metabolism in auditory function and the underlying mechanisms remain unclear. Our results reveal that the neomycin exposure disrupts lipid metabolism in auditory system. We find that neomycin-induced hair cells (HC) damage leads to abnormal lipid droplets (LD) accumulation. Further research reveals that decreased YAP expression is a key factor that contributes to abnormal LD accumulation. In both in vivo and in vitro studies, Yap overexpression reduces abnormal LD accumulation and mitigated HC damage. To further investigate its downstream mechanisms, we perform a cross-analysis of Yap-related and lipid metabolism–related genes, identifying that Cox2 is a key downstream target of Yap that contributes to LD accumulation and HC damage. Our work provides clear evidence for the role of lipid metabolism in neomycin-induced hearing loss and elucidates underlying mechanism of Yap/Cox2 pathway. These findings provide new perspectives and avenues for the clinical treatment of sensorineural hearing loss.

Data availability

The materials described in the manuscript, including all relevant raw data, will be freely available to any researcher wishing to use them for non-commercial purposes, without breaching participant confidentiality.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (82271173, 82192862, 82371157, and 82371156), the Natural Science Foundation of Jiangsu Province (BE2023653 and BK20230052), the Jiangsu Provincial Medical Key Discipline (Laboratory) (ZDXK202243), and the research grant from MOE key laboratory of model animal for disease study.

Author information

Author notes

  1. These authors contributed equally: Wenli Hao, Song Gao.

Authors and Affiliations

  1. Department of Otolaryngology-Head and Neck Surgery, Jiangsu Provincial Key Medical Discipline (Laboratory), Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China

    Wenli Hao, Song Gao, Suhan Guo, Jingjing Luo, Siyu Li, Junze Lu, Nan Wang, Aijia Ran, Xiaoyun Qian, Xia Gao, Chenjie Yu & Cheng Cheng

  2. Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing, China

    Lulu Jiang

  3. Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou, China

    Jie Lu

  4. Research Institute of Otolaryngology, Nanjing, China

    Xiaoyun Qian, Xia Gao, Chenjie Yu & Cheng Cheng

  5. Department of Otolaryngology-Head and Neck Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, MOE Key Laboratory of Model Animal for Disease Study, Nanjing University, Nanjing, China

    Cheng Cheng

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Contributions

Conceptualization and methodology: CC, CY, XG, and XQ; Bioinformatics analysis: WH and Song Gao; in vitro and in vivo experiments: WH and SL; Data analysis and interpretation: WH, Jie Lu, Jinging Luo, Lulu Jiang, and Suhan Guo; Manuscript writing: WH, Junze Lu, NW, and AR; Manuscript review and editing: CC, CY, XG, and XQ; Supervision: XG and CC. All authors have read and approved the final version of the manuscript.

Corresponding authors

Correspondence to Xiaoyun Qian, Xia Gao, Chenjie Yu or Cheng Cheng.

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The authors declare no competing interests.

Ethics approval and consent to participate

All animal experimental procedures received approval from the Animal Care and Use Committee of Nanjing University (2025AE01009) and were performed in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals.

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Hao, W., Gao, S., Guo, S. et al. Regulation of lipid droplets accumulation by the Hippo–YAP/COX2 signaling pathway in neomycin-induced ototoxicity. Cell Death Discov. (2026). https://doi.org/10.1038/s41420-026-03115-w

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  • Received: 07 November 2025

  • Revised: 16 March 2026

  • Accepted: 01 April 2026

  • Published: 16 April 2026

  • DOI: https://doi.org/10.1038/s41420-026-03115-w

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