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Regulation of PTEN and ovarian cancer progression by an E3 ubiquitin ligase RBCK1

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Abstract

Ovarian cancer is one of the most lethal gynecologic malignancies worldwide, with the 5-year survival is less than 50%. Although some clinical achievements have been achieved, the overall survival rate has remained unchanged over the past 20 years. Therefore, it is necessary and urgent to develop the potential modifiers and therapeutic approach to improve the overall survival rate in ovarian cancer patients. RBCK1 is an RING protein E3 ubiquitin ligase, which was revealed to involve in the progression of several cancers through its ubiquitination function. In this research, we report that RBCK1 expression is significantly elevated in human ovarian cancer and strongly associated with poor patients’ prognosis. RBCK1 deficiency induces cell apoptosis and inhibits cell proliferation and migration in ovarian cancer cells. In terms of molecular mechanism, we report that RBCK1 interacts with PTEN and promotes PTEN degradation in K48-linked ubiquitination. Our study suggests a new and interesting regulatory mechanism that RBCK1 facilitates PTEN degradation, which could be a new potential therapeutic target for ovarian cancer treatment.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank all the members of Department of Gynaecology and Obstetrics, Affiliated Hospital of Xuzhou Medical University for sharing valuable material and research support.

Funding

This project were supported by Natural Science Foundation of Jiangsu Province (Grant No. BK20181152), China Postdoctoral Science Foundation funded project (Grant No. 237399), Scientific Research Project of Jiangsu Commission of Health (No. H2018015), Primary Research and Development Plan of Xuzhou Science and Technology (No. KC18146; No. KC20166), Research Project of Jiangsu Maternal and Child Health (No. F201903), Research and innovation program for Postgraduates in Colleges and universities in Jiangsu Province (No. KYCX20_2483), the Key Laboratory Foundation of Jiangsu Province (No. XZSYSKF2021017), and the Development Fund of Affiliated Hospital of Xuzhou Medical University (No. XYFM2021009).

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Author notes

  1. Guanghui Wang, Zi Zhuang, and Siyuan Shen have contributed equally to this work.

Authors and Affiliations

  1. Department of Gynaecology and Obstetrics, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China

    Guanghui Wang

  2. Graduate School, Xuzhou Medical University, Xuzhou, China

    Zi Zhuang

  3. Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, China

    Siyuan Shen, Fan Yang & Zhiyuan Jiang

  4. Department of General Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China

    Ziping Liu & Tianshi Wang

  5. Department of Neurosurgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China

    Lei Hua

Authors
  1. Guanghui Wang
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  4. Fan Yang
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  8. Lei Hua
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Contributions

LH conceived and designed the study. GW, ZZ, and SS collected and wrote the manuscript. FY and ZJ helped to analyze the data. ZL and TW supervised the present study and had full access to all the data. LH confirm the authenticity of all the raw data. All authors read and approved the final manuscript.

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Correspondence to Lei Hua.

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The authors declare that there is no conflict of interest.

Ethics approval

Approval was obtained from the ethics committee of University Affiliated Hospital of Xuzhou Medical University (No. XYFY2021-KL017-01). The procedures used in this study adhere to the tenets of the Declaration of Helsinki.

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Wang, G., Zhuang, Z., Shen, S. et al. Regulation of PTEN and ovarian cancer progression by an E3 ubiquitin ligase RBCK1. Human Cell 35, 896–908 (2022). https://doi.org/10.1007/s13577-022-00681-w

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  • DOI: https://doi.org/10.1007/s13577-022-00681-w

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