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Knockdown of FBXO22 inhibits melanoma cell migration, invasion and angiogenesis via the HIF-1α/VEGF pathway

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Summary

F-box proteins, a type of substrate-recognition complexes consisting of SKP1-cullin 1-F-box protein (SCF) E3 ligase, can critically affect many cellular processes because of the ubiquitylation and subsequent degradation of target proteins. This study investigated the effect of FBXO22 on melanoma angiogenesis, migration, and invasion. Results showed that FBXO22 staining intensity was increased in malignant melanoma (MM) compared with that in skin tissue (P˂0.001). The percentage of high FBXO22 expression in MM (74.3%) was markedly higher than that in paracancerous and skin tissues (0%) (P˂0.001). FBXO22 was also overexpressed in MM tissues compared with that in normal skin tissues. FBXO22 knockdown in vitro inhibited MM cell migration, invasion, and angiogenesis (P < 0.001). In vivo studies confirmed that using nude mice with knocked down FBXO22 reduced the formation of blood vessels and decreased the positive rate of CD31 (P < 0.05). HIF-1α expression varied with FBXO22, indicating that FBXO22 regulated the expression of HIF-1α and VEGFA and that FBXO22 was a regulator of HIF-1α and VEGF for the control of tumor angiogenesis. In conclusion, FBXO22 promoted the migration and invasion of tumor cells and melanoma angiogenesis via HIF-1α upregulation. This study demonstrated that FBXO22 knockdown suppressed tumor progression and metastasis, suggesting that FBXO22 might be developed as a novel target for treating patients with MM.

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Funding

This study was funded by grants from the National Natural Science Foundation of China (No. 81672845, 81872304), the Project of Invigorating Health Care through Science, Technology and Education from Jiangsu Province (ZDRCC2016009), the Priority Academic Program for the Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine).

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Authors and Affiliations

  1. Department of Plastic Surgery, The Affiliated Friendship Plastic Surgery Hospital with Nanjing Medical University, 149 Hanzhong Road, Nanjing, 210029, Jiangsu Province, China

    Yufan Zheng, Yang Zhao & Hongwei Zhang

  2. Department of Plastic Surgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu Province, China

    Yufan Zheng

  3. Department of Occupational Medicine and Environmental Health, School of Public Health, Nanjing Medical University, Nanjing, 210029, Jiangsu Province, China

    Hairong Chen

  4. Cancer Institute, Xuzhou Medical University, Xuzhou, 221002, Jiangsu Province, China

    Xuping Zhang, Jinjin Liu, Yu Pan & Jin Bai

  5. Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, 221002, Jiangsu Province, China

    Jin Bai

  6. Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical University, 84 West Huaihai Road, Xuzhou, 221002, Jiangsu Province, China

    Jin Bai

Authors
  1. Yufan Zheng
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  2. Hairong Chen
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  3. Yang Zhao
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  4. Xuping Zhang
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  5. Jinjin Liu
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  6. Yu Pan
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  7. Jin Bai
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  8. Hongwei Zhang
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Corresponding authors

Correspondence to Jin Bai or Hongwei Zhang.

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The authors have declared that no competing interest exists.

Ethical approval

All experiments involved in this study were approved by both the Institutional Review Boards of Xuzhou Medical University and the Ethics Committee of the above hospital.

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Each patient provided a written informed consent prior to the study.

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Yufan Zheng and Hairong Chen contributed equally to this work.

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Zheng, Y., Chen, H., Zhao, Y. et al. Knockdown of FBXO22 inhibits melanoma cell migration, invasion and angiogenesis via the HIF-1α/VEGF pathway. Invest New Drugs 38, 20–28 (2020). https://doi.org/10.1007/s10637-019-00761-z

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  • DOI: https://doi.org/10.1007/s10637-019-00761-z

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