MiR-33a suppresses breast cancer cell proliferation and metastasis by targeting ADAM9 and ROS1

Protein Cell. 2015 Dec;6(12):881-9. doi: 10.1007/s13238-015-0223-8. Epub 2015 Oct 27.


MicroRNAs (miRNAs) are small noncoding RNAs that have a pivotal role in the post-transcriptional regulation of gene expression by sequence-specifically targeting multiple mRNAs. Although miR-33a was recently reported to play an important role in lipid homeostasis, atherosclerosis, and hepatic fibrosis, the functions of miR-33a in tumor progression and metastasis are largely unknown. Here, we found that downregulated miR-33a in breast cancer tissues correlates with lymph node metastasis. MiR-33a expression is significantly lower in the highly metastatic breast cancer cell lines than the noncancerous breast epithelial cells and non-metastatic breast cancer cells. Moreover, the overexpression of miR-33a in metastatic breast cancer cells remarkably decreases cell proliferation and invasion in vitro and significantly inhibits tumor growth and lung metastasis in vivo, whereas its knockdown in non-metastatic breast cancer cells significantly enhances cell proliferation and invasion in vitro and promotes tumor growth and lung metastasis in vivo. Combining bioinformatics prediction and biochemical analyses, we showed that ADAM9 and ROS1 are direct downstream targets of miR-33a. These findings identified miR-33a as a negative regulator of breast cancer cell proliferation and metastasis.

Keywords: breast cancer; metastasis; miR-33a; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / deficiency
  • ADAM Proteins / genetics*
  • Animals
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Female
  • Humans
  • Lung Neoplasms / secondary
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics*
  • Mice
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Protein-Tyrosine Kinases / deficiency
  • Protein-Tyrosine Kinases / genetics*
  • Proto-Oncogene Proteins / deficiency
  • Proto-Oncogene Proteins / genetics*


  • MIRN33a microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • Proto-Oncogene Proteins
  • Protein-Tyrosine Kinases
  • ROS1 protein, human
  • ADAM Proteins
  • ADAM9 protein, human