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.
Purpose:
Although histone deacetylase (HDAC) inhibitors have been shown to effectively induce the inhibition of proliferation and migration in breast cancer, the mechanism of HDAC9's contribution to chemoresistance remains poorly understood. The aim of this study was to investigate the role of miR-30c-regulated HDAC9 in chemoresistance of breast cancer and to determine the potential of selective inhibition of HDAC9 in sensitizing resistant breast cancer cells to chemotherapy.
Methods:
Expression levels of HDAC9 and miR-30c were measured in breast cancer cells and tissues using quantitative PCR analysis. The effect of selective inhibition of HDAC9 on sensitizing MDR cells to chemotherapy was assessed. MiR-30c/HDAC9 pathways' potential to mediate chemoresistance was analyzed.
Results:
Our studies show that HDAC9 was significantly up-regulated in chemoresistant breast cancer cell lines compared to a chemosensitive cell line and was inversely correlated with the levels of miR-30c. MiR-30c mimics and HDAC9 inhibitors reversed the chemoresistance of multidrug-resistant breast cancer cells.
Conclusions:
These results indicate that the mechanism of chemoresistance reversal with selective HDAC inhibition was partially realized by regulating miR-30c via directly targeting HDAC9. Our findings suggest that the miR-30c/HDAC9 signaling axis could be a novel and potential therapeutic target in chemoresistant breast cancer.
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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