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Published on: September 18, 2013

Suppression of miRNA-708 by polycomb group promotes metastases by calcium-induced cell migration

Seongho Ryu1, Kevin McDonnell, Hyejin Choi

  • 1Department of Cardiothoracic Surgery, Weill Cornell Medical College of Cornell University, New York, NY 10065, USA.

Cancer Cell
|January 19, 2013
PubMed

Insights

MicroRNA-708 (miR-708) suppresses breast cancer metastasis by targeting neuronatin, reducing cell migration and invasion. Lower miR-708 levels correlate with metastasis in patients, indicating its therapeutic potential.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Metastatic breast cancer remains a leading cause of cancer-related mortality.
  • Understanding the molecular mechanisms driving metastasis is crucial for developing effective therapies.

Purpose of the Study:

  • To investigate the role of microRNA-708 (miR-708) in breast cancer metastasis.
  • To elucidate the regulatory mechanisms and downstream targets of miR-708 in the context of metastasis.

Main Methods:

  • Analysis of miR-708 expression in breast cancer tissues.
  • Investigating the role of Polycomb Repressor Complex 2 (PRC2) in miR-708 repression.
  • Identifying miR-708 targets and their functional consequences on cell migration and metastasis.
  • In vitro and in vivo models of breast cancer metastasis.

Main Results:

  • miR-708 is transcriptionally repressed by PRC2-mediated H3K27 trimethylation in metastatic breast cancer.
  • miR-708 directly targets neuronatin, decreasing intracellular calcium levels.
  • Reduced neuronatin levels impair activation of ERK and FAK, leading to decreased cell migration and metastasis.
  • Ectopic expression of miR-708 suppressed metastasis, while neuronatin overexpression rescued these defects.
  • miR-708 expression is significantly decreased in lymph node and distal metastases of breast cancer patients.

Conclusions:

  • miR-708 acts as a metastasis suppressor in breast cancer by regulating the neuronatin-calcium-ERK/FAK pathway.
  • PRC2-mediated repression of miR-708 contributes to breast cancer progression and metastasis.
  • miR-708 represents a potential therapeutic target for combating metastatic breast cancer.

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