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Cited by 72Ubiquitin and proteasome pathwaysLung Cancer Research StudiesProtein Degradation and Inhibitors

USP7 promotes cell proliferation through the stabilization of Ki-67 protein in non-small cell lung cancer cells.

Zhang, Chao, Lu, Jing, Zhang, Quan-Wu, Zhao, Wei, Guo, Jia-Hui, Liu, Shan-Ling, Wu, Ying-Li, Jiang, Bin +1 more·2016·The International Journal of Biochemistry & Cell Biology
DOI 10.1016/j.biocel.2016.08.025
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Abstract

The Ki-67 antigen (Ki-67) is the most reliable immunohistochemical marker for evaluation of cell proliferation in non-small cell lung cancer. However, the mechanisms underlying the regulation of protein levels of Ki-67 in non-small cell lung cancer have remained elusive. In this study, we found that Ki-67 and ubiquitin-specific processing protease 7 (USP7) protein were highly expressed in the nucleus of non-small cell lung cancer cells. Furthermore, statistical analysis uncovered the existence of a strong correlation between Ki-67 and USP7 levels. We could also show that the protein levels of Ki-67 in non-small cell lung cancer cells significantly decreased after treatment with P22077, a selective chemical inhibitor of USP7, while the Ki-67 mRNA levels were unperturbed. Similar results were obtained by knocking down USP7 using short hairpin RNA (shRNA) in lung cancer cells. Interestingly, we noticed that ubiquitination levels of Ki-67 increased dramatically in USP7-silenced cells. The tests in vitro and vivo showed a significant delay in tumor cell growth upon knockdown of USP7. Additionally, drug sensitivity tests indicated that USP7-silenced A549 cells had enhanced sensitivity to paclitaxel and docetaxel, while there was no significant change in sensitivity toward carboplatin and cisplatin. Taken together, these data strongly suggest that the overexpression of USP7 might promote cell proliferation by deubiquitinating Ki-67 protein, thereby maintaining its high levels in the non-small cell lung cancer. Our study also hints potential for the development of deubiquitinase-based therapies, especially those targeting USP7 to improve the condition of patients diagnosed with non-small cell lung cancer.

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Crossref · 10.1016/j.biocel.2016.08.025

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  • USP7 might contribute to oncogenesis by deubiquitinating and stabilizing Ki-67.

    “USP7 might also contribute to oncogenesis by deubiquitinating and stabilizing Ki-67 (Zhang et al., 2016).”

    From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Zhang et al., 2016

  • A strong positive correlation between USP7 and Ki-67 has been observed in non-small cell lung cancer cells.

    “This interaction may be particular disease-relevant in non-small cell lung cancer cells, where a strong positive correlation between the two proteins has been observed (Zhang et al., 2016).”

    From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Zhang et al., 2016

  • Another proposed use for USP7 inhibitors is in sensitizing taxane-resistant tumors to taxane therapies.

    “Another proposed use for USP7 inhibitors is in sensitizing taxane-resistant tumors to taxane therapies (Giovinazzi et al., 2013; Zhang et al., 2016; Peng et al., 2019).”

    From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Zhang et al., 2016

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Authors
Zhang, C., Lu, J., Zhang, Q.-W., Zhao, W., Guo, J.-H., Liu, S.-L., Wu, Y.-L., Jiang, B., & Gao, F.-H.
Affiliations
  • Shanghai Jiao Tong University (CN)
  • Zhengzhou University (CN)
  • Soochow University (CN)
Corresponding author
  • Jiang, Bin
  • Gao, Feng-Hou
ORCID
Venue
The International Journal of Biochemistry & Cell Biology
Publisher
Elsevier BV
Published
2016-10
Volume
79
Pages
209-221
ISSN
1357-2725 (ISSN-L)
DOI
10.1016/j.biocel.2016.08.025
OpenAlex
W2517329137
Cited by
67
References
57
Citations by year
2026: 2 · 2025: 8 · 2024: 3 · 2023: 7 · 2022: 3 · 2021: 12 · 2020: 17 · 2019: 7 · 2018: 5 · 2017: 3
FWCI
2.60
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • The International Journal of Biochemistry & Cell Biology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (81172322, 81302006)
  • Shanghai Municipal Education Committee (13ZZ089)
  • Science and Technology Committee of Shanghai (14401901500)
  • Science and Technology Committee of Baoshan District (12-E-2)
  • Science and Technology of Henan province fund (142102310461)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
  • Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
Keywords
USP7, Ki-67, non-small cell lung cancer, cell proliferation, protein stabilization, deubiquitination, ubiquitination, paclitaxel sensitivity, docetaxel sensitivity, deubiquitinase inhibitors, A549 cells
MeSH terms
Ubiquitin-Specific Peptidase 7, Animals, Carcinoma, Non-Small-Cell Lung, Cell Transformation, Neoplastic, Female, Humans, Lung Neoplasms, Male, Middle Aged, Up-Regulation, Ki-67 Antigen, Cytoprotection, Cell Line, Tumor, Cell Proliferation, Mice, Protein Stability, Gene Knockdown Techniques

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