Tumor Biology

, Volume 36, Issue 4, pp 2875–2883 | Cite as

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

  • Yue Gao
  • Fan Zeng
  • Jia-Yan Wu
  • Hai-Yu Li
  • Jian-Jun Fan
  • Li Mai
  • Ji Zhang
  • Dong-Mei Ma
  • Yun Li
  • Fang-zhou Song
Research Article

Abstract

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.

Keywords

Breast cancer miR-335 c-Met HGF Metastasis 5-AZA-CdR 

Notes

Acknowledgments

This research is supported by the Doctoral Fund of Ministry of Education of China (No. 20125503110012).

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Yue Gao
    • 1
  • Fan Zeng
    • 1
  • Jia-Yan Wu
    • 1
  • Hai-Yu Li
    • 1
  • Jian-Jun Fan
    • 1
  • Li Mai
    • 1
  • Ji Zhang
    • 1
  • Dong-Mei Ma
    • 1
  • Yun Li
    • 1
  • Fang-zhou Song
    • 1
    • 2
  1. 1.Molecular Medicine & Cancer Research Center, College of Basic MedicineChongqing Medical UniversityChongqingChina
  2. 2.Department of Biochemistry & Molecular Biology, College of Basic MedicineChongqing Medical UniversityChongqingChina

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