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Combating breast cancer progression through combination therapy with hypomethylating agent and glucocorticoid

Yu-Hsin Chu1, Yi-Chen Huang1, Pei-Yun Chiu1

  • 1Institute of Biotechnology, College of Life Science, National Tsing Hua University, Hsinchu, Taiwan.

Iscience
|May 2, 2023
PubMed

Insights

This study found that low microRNA-708 expression is linked to poor prognosis in triple-negative breast cancer (TNBC). Combining decitabine with glucocorticoid therapy may offer a new treatment strategy for TNBC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis.
  • MicroRNA-708 (miR-708) promoter methylation correlates with poor outcomes in breast cancer.
  • Restoring miR-708 expression shows potential for improving TNBC patient outcomes.

Purpose of the Study:

  • To investigate the role of microRNA-708 in triple-negative breast cancer.
  • To evaluate the therapeutic potential of combining decitabine and glucocorticoid in TNBC.

Main Methods:

  • Bioinformatic analysis of microRNA-708 promoter methylation in breast cancer.
  • In vitro studies assessing the effects of decitabine and glucocorticoid combination therapy on TNBC cell lines.
  • In vivo studies using a TNBC xenograft mouse model to evaluate tumor growth and metastasis.

Main Results:

  • MicroRNA-708 promoter methylation was associated with poor prognosis in breast cancer.
  • Combination treatment with decitabine and glucocorticoid increased miR-708 expression and suppressed metastasis-promoting genes (MMPs, IL-1β).
  • The combined regimen reduced TNBC cell proliferation, migration, invasion, tumor growth, and distant metastasis in mice.

Conclusions:

  • MicroRNA-708 acts as a tumor suppressor in TNBC.
  • Combined decitabine and glucocorticoid therapy demonstrates significant therapeutic potential for TNBC by reactivating tumor suppressor pathways and inhibiting metastasis.
  • This combination represents a promising novel therapeutic strategy for TNBC patients.
Keywords:
CancerEpigeneticsMolecular biology

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