Suppression of miRNA-708 by polycomb group promotes metastases by calcium-induced cell migration. Academic Article uri icon

Overview

abstract

  • The progression of cancer to metastatic disease is a major cause of death. We identified miR-708 being transcriptionally repressed by polycomb repressor complex 2-induced H3K27 trimethylation in metastatic breast cancer. miR-708 targets the endoplasmic reticulum protein neuronatin to decrease intracellular calcium level, resulting in reduction of activation of ERK and FAK, decreased cell migration, and impaired metastases. Ectopic expression of neuronatin refractory to suppression by miR-708 rescued cell migration and metastasis defects. In patients with breast cancer, miR-708 expression was decreased in lymph node and distal metastases, suggesting a metastasis-suppressive role. Our findings uncover a mechanistic role for miR-708 in metastasis and provide a rationale for developing miR-708 as a therapeutic agent against metastatic breast cancer.

publication date

  • January 14, 2013

Research

keywords

  • Breast Neoplasms
  • Calcium
  • Gene Expression Regulation, Neoplastic
  • Membrane Proteins
  • MicroRNAs
  • Neoplasm Metastasis
  • Nerve Tissue Proteins
  • Polycomb-Group Proteins

Identity

Scopus Document Identifier

  • 84872376809

Digital Object Identifier (DOI)

  • 10.1016/j.ccr.2012.11.019

PubMed ID

  • 23328481

Additional Document Info

volume

  • 23

issue

  • 1