MiR-335 inhibits migration of breast cancer cells through targeting oncoprotein c-Met

Tumour Biol. 2015 Apr;36(4):2875-83. doi: 10.1007/s13277-014-2917-6. Epub 2014 Dec 10.


Metastasis is the leading cause of death in patients with breast cancer and aberrantly expressed microRNAs (miRNAs) are highly associated with this process. A previous study has shown that miR-335 is downregulated in breast cancer and can suppress tumor invasion and metastasis. Emerging evidences indicate that c-Met is implicated in cell scattering, migration, and invasion. However, little is known about the relationship between miR-335 expression and c-Met alteration in breast cancer. In the present study, we found that miR-335 expression was downregulated and c-Met protein expression was upregulated in two human breast cell lines. MiR-335 was found to negatively regulate c-Met protein level by directly targeting its 3' untranslated region (UTR). Forced expression of miR-335 decreased c-Met expression at protein levels and consequently diminished hepatocyte growth factor (HGF)-induced phosphorylation of c-Met and subsequently inhibited HGF promotion of breast cancer cell migration in a c-Met-dependent manner. MiR-335 expression was increased after 5-aza-2'-deoxycytidine (5-AZA-CdR) treatment, and 5-AZA-CdR treatment resulted in the same phenotype as the effect of miR-335 overexpression. Taken together, these results demonstrate that miR-335 suppresses breast cancer cell migration by negatively regulating the HGF/c-Met pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Azacitidine / administration & dosage
  • Azacitidine / analogs & derivatives
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Movement / drug effects
  • Cell Proliferation / genetics
  • Decitabine
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Hepatocyte Growth Factor / metabolism*
  • Humans
  • MCF-7 Cells
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Neoplasm Invasiveness / genetics
  • Proto-Oncogene Proteins c-met / biosynthesis*
  • Proto-Oncogene Proteins c-met / genetics


  • MIRN335 microRNA, human
  • MicroRNAs
  • Hepatocyte Growth Factor
  • Decitabine
  • Proto-Oncogene Proteins c-met
  • Azacitidine