miR-145-dependent targeting of junctional adhesion molecule A and modulation of fascin expression are associated with reduced breast cancer cell motility and invasiveness

Oncogene. 2010 Dec 16;29(50):6569-80. doi: 10.1038/onc.2010.386. Epub 2010 Sep 6.


Micro RNAs are small non-coding RNAs, which regulate fundamental cellular and developmental processes at the transcriptional and translational level. In breast cancer, miR-145 expression is downregulated compared with healthy control tissue. As several predicted targets of miR-145 potentially regulate cell motility, we aimed at investigating a potential role for miR-145 in breast cancer cell motility and invasiveness. Assisted by Affymetrix array technology, we demonstrate that overexpression of miR-145 in MDA-MB-231, MCF-7, MDA-MB-468 and SK-BR-3 breast cancer cells and in Ishikawa endometrial carcinoma cells leads to a downregulation of the cell-cell adhesion protein JAM-A and of the actin bundling protein fascin. Moreover, podocalyxin and Serpin E1 mRNA levels were downregulated, and gamma-actin, transgelin and MYL9 were upregulated upon miR-145 overexpression. These miR-145-dependent expression changes drastically decreased cancer cell motility, as revealed by time-lapse video microscopy, scratch wound closure assays and matrigel invasion assays. Immunofluorescence microscopy demonstrated restructuring of the actin cytoskeleton and a change in cell morphology by miR-145 overexpression, resulting in a more cortical actin distribution, and reduced actin stress fiber and filopodia formation. Nuclear rotation was observed in 10% of the pre-miR-145 transfected MDA-MB-231 cells, accompanied by a reduction of perinuclear actin. Luciferase activation assays confirmed direct miR-145-dependent regulation of the 3'UTR of JAM-A, whereas siRNA-mediated knockdown of JAM-A expression resulted in decreased motility and invasiveness of MDA-MB-231 and MCF-7 breast cancer cells. Our data identify JAM-A and fascin as novel targets of miR-145, firmly establishing a role for miR-145 in modulating breast cancer cell motility. Our data provide a rationale for future miR-145-targeted approaches of antimetastatic cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / analysis
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Carrier Proteins / metabolism*
  • Cell Adhesion Molecules / metabolism*
  • Cell Line, Tumor
  • Cell Movement*
  • Cytoskeleton
  • Down-Regulation
  • Female
  • Humans
  • Immunoglobulins / metabolism*
  • MicroRNAs / metabolism*
  • Microfilament Proteins / analysis
  • Microfilament Proteins / metabolism*
  • Muscle Proteins / analysis
  • Neoplasm Invasiveness
  • Plasminogen Activator Inhibitor 1 / analysis
  • Receptors, Cell Surface
  • Sialoglycoproteins / analysis


  • Actins
  • Carrier Proteins
  • Cell Adhesion Molecules
  • F11R protein, human
  • Immunoglobulins
  • MIRN145 microRNA, human
  • MicroRNAs
  • Microfilament Proteins
  • Muscle Proteins
  • Plasminogen Activator Inhibitor 1
  • Receptors, Cell Surface
  • Sialoglycoproteins
  • podocalyxin
  • transgelin
  • fascin