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Background <p>Cervical cancer poses a significant threat to women’s health, and its metastasis is one of the leading causes of cancer-related deaths. Tubeimoside I (TBMS1) is a traditional Chinese medicinal herb with anticancer properties. We previously demonstrated the anticancer effect of TBMS1 in cervical cancer by inducing autophagy-related cell death. Nevertheless, whether and how TBMS1 prevents cervical cancer metastasis remain unclear.</p> Methods <p>Wound healing, transwell assays, and a lung metastasis mouse model were used to evaluate cell metastasis. Immunoprecipitation combined with site-directed mutagenesis was used to explore ubiquitination modifications and ubiquitinated sites of histone deacetylase 5 (HDAC5). HDAC5 depletion and RNA-seq analysis were conducted to investigate the anti-metastatic mechanism of TBMS1.</p> Results <p>We show that low dose of TBMS1 inhibits cervical cancer metastasis. Mechanistically, TBMS1 binds to HDAC5 and prevents HDAC5 ubiquitination at lysine 137 and 538, leading to a decrease in proteasomal degradation of HDAC5. TBMS1-mediated HDAC5 upregulation further reduces the acetylation level of histone H3 lysine 27 (H3K27ac) and suppresses KPNA2 expression. HDAC5 depletion significantly attenuates TBMS1’s anti-metastatic effect in cervical cancer.</p> Conclusion <p>Our study reveals HDAC5/H3K27ac/KPNA2 axis as the anti-metastatic mechanism of TBMS1 in cervical cancer, suggesting TBMS1 serves as a promising drug for cervical cancer treatment.</p>

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HDAC5 stabilization by tubeimoside I suppresses cervical cancer metastasis via inhibiting H3K27ac/KPNA2 axis

  • 期刊论文

  • 发表日期：

    2026年1月8日

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  • Mao Wang,
  • Jiawu Fan,
  • Baoquan Mu,
  • Yan Zeng,
  • Yixuan Sun,
  • Heyang Zhang,
  • Lixia Dong,
  • Sinan Lv,
  • Sijia Li,
  • Xuejiao Ma,
  • Dingrui Chen,
  • Chunhui Yu,
  • Li Luo,
  • Changlong Li,
  • Kui Wang

摘要

Background

Cervical cancer poses a significant threat to women’s health, and its metastasis is one of the leading causes of cancer-related deaths. Tubeimoside I (TBMS1) is a traditional Chinese medicinal herb with anticancer properties. We previously demonstrated the anticancer effect of TBMS1 in cervical cancer by inducing autophagy-related cell death. Nevertheless, whether and how TBMS1 prevents cervical cancer metastasis remain unclear.

Methods

Wound healing, transwell assays, and a lung metastasis mouse model were used to evaluate cell metastasis. Immunoprecipitation combined with site-directed mutagenesis was used to explore ubiquitination modifications and ubiquitinated sites of histone deacetylase 5 (HDAC5). HDAC5 depletion and RNA-seq analysis were conducted to investigate the anti-metastatic mechanism of TBMS1.

Results

We show that low dose of TBMS1 inhibits cervical cancer metastasis. Mechanistically, TBMS1 binds to HDAC5 and prevents HDAC5 ubiquitination at lysine 137 and 538, leading to a decrease in proteasomal degradation of HDAC5. TBMS1-mediated HDAC5 upregulation further reduces the acetylation level of histone H3 lysine 27 (H3K27ac) and suppresses KPNA2 expression. HDAC5 depletion significantly attenuates TBMS1’s anti-metastatic effect in cervical cancer.

Conclusion

Our study reveals HDAC5/H3K27ac/KPNA2 axis as the anti-metastatic mechanism of TBMS1 in cervical cancer, suggesting TBMS1 serves as a promising drug for cervical cancer treatment.