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HMGB3 small interfere RNA suppresses mammosphere formation of MDA-MB-231 cells by down-regulating expression of HIF1α

J Gu1, T Xu, C-M Zhang

  • 1Department of Health Check-Up Center, Jinshan Hospital, Fudan University, Shanghai, China. liuzheef@sina.com.

European Review for Medical and Pharmacological Sciences
|November 28, 2019
PubMed
Abstract

Insights

High-mobility group box 3 (HMGB3) small interfering RNA (siRNA) inhibits breast cancer cell proliferation. HMGB3-siRNA suppresses mammosphere formation by downregulating hypoxia-inducible factor 1α (HIF1α) expression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • Breast cancer is a prevalent malignancy affecting women globally.
  • High-mobility group box 3 (HMGB3) is implicated in various cancers.
  • Understanding HMGB3's role in breast cancer proliferation is crucial for therapeutic development.

Purpose of the Study:

  • To investigate the effect of HMGB3-siRNA on breast cancer cell proliferation.
  • To elucidate the underlying molecular mechanisms involving HMGB3, stem cell markers, and HIF1α.

Main Methods:

  • HMGB3-siRNA lentiviral vectors were transfected into breast cancer cells (MDA-MB-231).
  • Cell proliferation was assessed using CCK-8 assays.
  • Mammosphere formation, stem cell marker expression (Nanog, Sox2, OCT-4), and CD44+/CD24- cell populations were evaluated.
  • The correlation and interaction between HMGB3 and HIF1α were analyzed.

Main Results:

  • HMGB3 expression was significantly elevated in breast cancer cells.
  • HMGB3-siRNA treatment reduced cell proliferation and mammosphere formation.
  • HMGB3-siRNA downregulated Nanog, Sox2, and OCT-4, while increasing CD44+/CD24- cells.
  • HMGB3-siRNA significantly decreased HIF1α expression, with a positive correlation observed between HMGB3 and HIF1α.

Conclusions:

  • HMGB3 small interfering RNA effectively suppresses breast cancer cell proliferation and mammosphere formation.
  • The observed effects are mediated through the downregulation of hypoxia-inducible factor 1α (HIF1α).
  • HMGB3 may represent a potential therapeutic target in breast cancer treatment.

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