MicroRNA-30c targets cytoskeleton genes involved in breast cancer cell invasion

Breast Cancer Res Treat. 2013 Jan;137(2):373-82. doi: 10.1007/s10549-012-2346-4. Epub 2012 Dec 7.

Abstract

Metastasis remains a significant challenge in treating cancer. A better understanding of the molecular mechanisms underlying metastasis is needed to develop more effective treatments. Here, we show that human breast tumor biomarker miR-30c regulates invasion by targeting the cytoskeleton network genes encoding twinfilin 1 (TWF1) and vimentin (VIM). Both VIM and TWF1 have been shown to regulate epithelial-to-mesenchymal transition. Similar to TWF1, VIM also regulates F-actin formation, a key component of cellular transition to a more invasive mesenchymal phenotype. To further characterize the role of the TWF1 pathway in breast cancer, we found that IL-11 is an important target of TWF1 that regulates breast cancer cell invasion and STAT3 phosphorylation. The miR-30c-VIM/TWF1 signaling cascade is also associated with clinical outcome in breast cancer patients.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cytoskeleton / genetics*
  • Cytoskeleton / pathology
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Interleukin-11 / genetics
  • Interleukin-11 / metabolism
  • Mice
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Microfilament Proteins / genetics*
  • Microfilament Proteins / metabolism
  • Molecular Sequence Data
  • Protein-Tyrosine Kinases / genetics*
  • Protein-Tyrosine Kinases / metabolism
  • Vimentin / genetics*
  • Vimentin / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • IL11 protein, human
  • Interleukin-11
  • MIRN30b microRNA, human
  • MicroRNAs
  • Microfilament Proteins
  • TWF1 protein, human
  • Vimentin
  • Protein-Tyrosine Kinases