Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Ginsenoside 20(S)-Rg3 reduces KIF20A expression and promotes CDC25A proteasomal degradation in epithelial ovarian cancer

  • Rong Zhang (Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital) ;
  • Lei Li (Department of Radiotherapy, People's Hospital of Shanxi Province) ;
  • Huihui Li (Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital) ;
  • Hansong Bai (Sichuan Cancer Hospital Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China) ;
  • Yuping Suo (Department of Gynecology and Obstetrics, People's Hospital of Shanxi Province) ;
  • Ju Cui (The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Science, Beijing Hospital/National Center of Gerontology of National Health Commission) ;
  • Yingmei Wang (Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital)
  • Received : 2022.11.16
  • Accepted : 2023.06.25
  • Published : 2024.01.01
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Abstract

Background: Ginsenoside 20(S)-Rg3 shows promising tumor-suppressive effects in ovarian cancer via inhibiting NF-kB signaling. This study aimed to explore the downstream tumor suppressive mechanisms of ginsenoside Rg3 via this signaling pathway. Materials and methods: A systematical screening was applied to examine the expression profile of 41 kinesin family member genes in ovarian cancer. The regulatory effect of ginsenoside Rg3 on KIF20A expression was studied. In addition, we explored interacting proteins of KIF20A and their molecular regulations in ovarian cancer. RNA-seq data from The Cancer Genome Atlas (TCGA) was used for bioinformatic analysis. Epithelial ovarian cancer cell lines SKOV3 and A2780 were used as in vitro and in vivo cell models. Commercial human ovarian cancer tissue arrays were used for immunohistochemistry staining. Results: KIF20A is a biomarker of poor prognosis among the kinesin genes. It promotes ovarian cancer cell growth in vitro and in vivo. Ginsenoside Rg3 can suppress the transcription of KIF20A. GST pull-down and co-immunoprecipitation (IP) assays confirmed that KIF20A physically interacts with BTRC (β-TrCP1), a substrate recognition subunit for SCFβ-TrCP E3 ubiquitin ligase. In vitro ubiquitination and cycloheximide (CHX) chase assays showed that via interacting with BTRC, KIF20A reduces BTRC-mediated CDC25A poly-ubiquitination and enhances its stability. Ginsenoside Rg3 treatment partly abrogates KIF20A overexpression-induced CDC25A upregulation. Conclusion: This study revealed a novel anti-tumor mechanism of ginsenoside Rg3. It can inhibit KIF20A transcription and promote CDC25A proteasomal degradation in epithelial ovarian cancer.

Keywords

Acknowledgement

This study was supported by Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-031A), Natural Science Foundation of Shanxi Province (grant no.202103021223422 and 202203021221261), and in part, by the National Natural Science Foundation of China (grant nos. 82073264).

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