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UBE2N inhibition abrogates cancer chemoresistance and metastasis in lung adenocarcinoma

Cancer Gene Therapy volume 32, pages 831–842 (2025)Cite this article

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Abstract

Chemoresistance and metastasis remain significant challenges in cancer therapy, resulting in treatment failures for cancer patients. Therefore, there is a need to investigate the mechanisms underlying cancer chemoresistance and metastasis, identify novel drug targets, and develop innovative antitumor medications. In this study, we have shown that the ubiquitin conjugating enzyme UBE2N plays a crucial role in promoting chemoresistance and metastasis in lung adenocarcinoma (LUAD) both in vitro and in vivo. Significantly, our study revealed that the natural compound wilforine functions as a potential inhibitor of UBE2N, effectively reversing resistance to cisplatin (CDDP) and inhibiting metastasis of LUAD both in vitro and in vivo. Our findings collectively suggest that UBE2N may have a pivotal role in the development of chemoresistance and metastasis in LUAD, providing a foundation for potential therapeutic strategies in the management of advanced cancer.

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Fig. 1: UBE2N confers LUAD chemoresistance to cisplatin in A549CDDP cells.
Fig. 2: UBE2N confers LUAD chemoresistance to cisplatin in A549 and H1299 cells.
Fig. 3: UBE2N confers LUAD chemoresistance to cisplatin in vivo.
Fig. 4: UBE2N promotes LUAD metastasis in vitro and in vivo.
Fig. 5: Wilforine inhibits UBE2N catalytic activity by targeting Cys87 residue.
Fig. 6: Wilforine chemosensitizes LUAD to cisplatin through targeting UBE2N in vitro.
Fig. 7: Wilforine chemosensitizes LUAD to cisplatin through targeting UBE2N in vivo.
Fig. 8: Wilforine inhibits LUAD metastasis through targeting UBE2N.

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Data availability

The data of this study are available from the corresponding author upon reasonable request.

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Funding

This work is supported by grants from the Jiangxi Provincial Natural Science Foundation (No. 20232ACB216013), the Ganpo Talent Support Project- Academic and technical leaders training programs in major disciplines (No. 20243BCE51154), the National Natural Science Foundation of China (No. 82203342), the Jiangxi Provincial Natural Science Foundation (No. 20224BAB216073, No. 20242BAB25336), and the Jiangxi Province Key Laboratory of Immunology and Inflammation (No. 2024SSY06251).

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Authors and Affiliations

  1. Institute of Clinical Medicine, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, China

    Zi-Mei Peng, Jin-Yong Xiong, Feng-Yi Deng, Chun-Xi Yang, Yan-Ru Chen & Zhen Zhang

  2. Centre for Medical Research and Translation, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, China

    Xing Wang

  3. Institute of Geriatrics, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, China

    Tao Wang & Xiao-Jian Han

  4. Jiangxi Province Key Laboratory of Immunology and Inflammation, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, China

    Zhen Zhang

Authors
  1. Zi-Mei Peng
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Contributions

Conceptualization, Zhen Zhang; Funding acquisition, Zhen Zhang, Chun-xi Yang; Investigation, Zi-Mei Peng, Jin-Yong Xiong, Feng-Yi Deng and Zhen Zhang; Methodology, Zi-Mei Peng and Feng-Yi Deng; Data curation, Zi-Mei Peng, Jin-Yong Xiong; Formal analysis, Zi-Mei Peng and Xing Wang; Project administration, Zhen Zhang, Xiao-jian Han; Supervision, Zhen Zhang, Xiao-jian Han; Validation, Xing Wang, Tao Wang, Chun-Xi Yang, Yan-Ru Chen; Writing – original draft, Zhen Zhang, Zi-Mei Peng; Writing – review & editing, Zhen Zhang, Xiao-jian Han.

Corresponding authors

Correspondence to Xiao-Jian Han or Zhen Zhang.

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The authors declare no competing interests.

Ethical approval

The animal experiments were approved by the Ethics Committee at the Jiangxi Provincial People’s Hospital (approval number: KT079). All methods were performed in accordance with the relevant guidelines and regulations.

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Peng, ZM., Xiong, JY., Deng, FY. et al. UBE2N inhibition abrogates cancer chemoresistance and metastasis in lung adenocarcinoma. Cancer Gene Ther 32, 831–842 (2025). https://doi.org/10.1038/s41417-025-00929-1

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