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Tropomodulin 3 Overexpression as a Marker for Platinum Resistance and Immune Infiltration in Ovarian Cancer
09:40

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HDAC2-Mediated SMAD7 Stabilisation Activates Wnt/β-Catenin Signalling to Drive DNA Damage Repair and Cisplatin

Yingying He1, Meiling Wu2, Xiaomin Xu2

  • 1Department of Pathology, Quzhou People's Hospital, The Quzhou Affiliated Hospital, Wenzhou Medical University, Quzhou, Zhejiang, China.

Journal of Cellular and Molecular Medicine
|August 4, 2026
PubMed

Insights

Histone deacetylase 2 (HDAC2) promotes cisplatin resistance in ovarian cancer by stabilizing SMAD7, activating Wnt/β-catenin signaling, and enhancing DNA repair. Reducing HDAC2 can overcome this resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Cisplatin resistance is a major challenge in ovarian cancer (OC) treatment.
  • The role of histone deacetylase 2 (HDAC2) in mediating this resistance remains unclear.

Purpose of the Study:

  • To elucidate the function of HDAC2 in cisplatin resistance in ovarian cancer.
  • To investigate the molecular mechanisms by which HDAC2 influences drug resistance and DNA repair.

Main Methods:

  • Utilized cisplatin-resistant OC cell lines with HDAC2 overexpression and knockdown models.
  • Performed chromatin immunoprecipitation, immunoprecipitation, and dual-luciferase reporter assays.
  • Analyzed gene expression via qRT-PCR and validated findings in a xenograft mouse model.

Main Results:

  • HDAC2 was highly expressed in cisplatin-resistant OC cells.
  • HDAC2 overexpression increased drug resistance and inhibited apoptosis and DNA damage.
  • HDAC2 deacetylated and stabilized SMAD7 protein, activating Wnt/β-catenin signaling and promoting DNA damage repair.

Conclusions:

  • HDAC2 enhances cisplatin resistance in ovarian cancer by stabilizing SMAD7.
  • The HDAC2/SMAD7 axis activates Wnt/β-catenin signaling and modulates DNA damage repair genes.
  • Targeting HDAC2 can overcome cisplatin resistance and inhibit tumor growth in OC.
Keywords:
DNA damage repairHDAC2SMAD7deacetylationovarian cancer

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