MicroRNA-30c-regulated HDAC9 mediates chemoresistance of breast cancer

Zhongxing Liang1,2, Amber Feng3, Hyunsuk Shim4,5

  • 1Department of Radiation Oncology, Emory University, Atlanta, GA, 30322, USA. zliang@emory.edu.

Abstract

Insights

This study reveals that high HDAC9 levels contribute to breast cancer chemoresistance. Inhibiting HDAC9, regulated by miR-30c, can resensitize resistant cells to chemotherapy, offering a new therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Histone deacetylase (HDAC) inhibitors show promise in breast cancer treatment.
  • The specific role of HDAC9 in chemoresistance is not well understood.

Purpose of the Study:

  • Investigate the role of miR-30c-regulated HDAC9 in breast cancer chemoresistance.
  • Evaluate the potential of selective HDAC9 inhibition to sensitize resistant breast cancer cells to chemotherapy.

Main Methods:

  • Quantitative PCR to measure HDAC9 and miR-30c expression in breast cancer cells and tissues.
  • Assessing the impact of selective HDAC9 inhibition on multidrug-resistant (MDR) cells.
  • Analyzing the miR-30c/HDAC9 pathway's role in mediating chemoresistance.

Main Results:

  • HDAC9 was significantly upregulated in chemoresistant breast cancer cells, inversely correlating with miR-30c levels.
  • MiR-30c mimics and HDAC9 inhibitors reversed chemoresistance in MDR breast cancer cells.

Conclusions:

  • Selective HDAC inhibition reverses chemoresistance partly by regulating miR-30c through direct targeting of HDAC9.
  • The miR-30c/HDAC9 signaling axis presents a potential therapeutic target for chemoresistant breast cancer.

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