Skip to main content

Advertisement

SpringerLink
Log in

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

  • Research Article
  • Published:
Tumor Biology

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–49.

    Article  PubMed  Google Scholar 

  2. Weigelt B, Peterse JL, van’t Veer LJ. Breast cancer metastasis: markers and models. Nat Rev Cancer. 2005;5:591–602.

    Article  CAS  PubMed  Google Scholar 

  3. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.

    Article  CAS  PubMed  Google Scholar 

  4. Costinean S, Zanesi N, Pekarsky Y, Tili E, Volinia S, Heerema N. Croce CM: Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in E(mu)-miR155 transgenic mice. Proc Natl Acad Sci U S A. 2006;103:7024–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Chen CZ, Li L, Lodish HF, Bartel DP. MicroRNAs modulate hematopoietic lineage differentiation. Science. 2004;303:83–6.

    Article  CAS  PubMed  Google Scholar 

  6. Zhao Y, Samal E, Srivastava D. Serum response factor regulates a muscle specific microRNA that targets Hand2 during cardiogenesis. Nature. 2005;436:214–20.

    Article  CAS  PubMed  Google Scholar 

  7. Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, et al. Croce CM: miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A. 2005;102:13944–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Esquela-Kerscher A, Slack FJ. Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer. 2006;6:259–69.

    Article  CAS  PubMed  Google Scholar 

  9. Tavazoie SF, Alarcón C, Oskarsson T, Padua D, Wang Q, Bos PD, et al. Endogenous human microRNAs that suppress breast cancer metastasis. Nature. 2008;451:147–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Valastyan S, Reinhardt F, Benaich N, Calogrias D, Szász AM, Wang ZC, et al. A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis. Cell. 2009;137:1032–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Ma L, Young J, Prabhala H, Pan E, Mestdagh P, Muth D, et al. Weinberg RA: miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nat Cell Biol. 2010;12:247–71.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Ma L, Teruya-Feldstein J, Weinberg RA. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature. 2007;449:682–8.

    Article  CAS  PubMed  Google Scholar 

  13. Birchmeier C, Birchmeier W, Gherardi E, Vande Woude GF. Met, metastasis, motility and more. Nat Rev Mol Cell Biol. 2003;4:915–25.

    Article  CAS  PubMed  Google Scholar 

  14. Benvenuti S, Comoglio PMJ. The MET receptor tyrosine kinase in invasion and metastasis. Cell Physiol. 2007;213:316–25.

    Article  CAS  Google Scholar 

  15. Leelawat K, Leelawat S, Tepaksorn P, Rattanasinganchan P, Leungchaweng A, Tohtong R, et al. Involvement of c-Met/hepatocyte growth factor pathway in cholangiocarcinoma cell invasion and its therapeutic inhibition with small interfering RNA specific for c-Met. J Surg Res. 2006;136:78–84.

    Article  CAS  PubMed  Google Scholar 

  16. Ma PC, Tretiakova MS, Nallasura V, Jagadeeswaran R, Husain AN, Salgia R, et al. Downstream signalling and specific inhibition of c-MET/HGF pathway in small cell lung cancer: implications for tumour invasion. Br J Cancer. 2007;97:368–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Sipeki S, Bander E, Buday L, Farkas G, Bácsy E, Ways DK, et al. Phosphatidylinositol 3-kinase contributes to Erk1/Erk2 MAP kinase activation associated with hepatocyte growth factor-induced cell scattering. Cell Signal. 1999;11:885–90.

    Article  CAS  PubMed  Google Scholar 

  18. Wu ZS, Wu Q, Wang CQ, Wang XN, Huang J, Zhao JJ, et al. Zhang N: miR-340 inhibition of breast cancer cell migration and invasion through targeting of oncoprotein c-Met. Cancer. 2011;117:2842–52.

    Article  CAS  PubMed  Google Scholar 

  19. Li N, Fu H, Tie Y, Hu Z, Kong W, Wu Y, et al. miR-34a inhibits migration and invasion by down-regulation of c-Met expression in human hepatocellular carcinoma cells. Cancer Lett. 2009;275:44–53.

    Article  CAS  PubMed  Google Scholar 

  20. Tan S, Li R, Ding K, Lobie PE, Zhu T. miR-198 inhibits migration and invasion of hepatocellular carcinoma cells by targeting the HGF/c-MET pathway. FEBS Lett. 2011;585:2229–34.

    Article  CAS  PubMed  Google Scholar 

  21. Krek A et al. Combinatorial microRNA target predictions. Nat Genet. 2005;37:495–500.

    Article  CAS  PubMed  Google Scholar 

  22. Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120:15–20.

    Article  CAS  PubMed  Google Scholar 

  23. Naldidi L, Vigna E, Narsimhan R, et al. Hepatocyte growth factor (HGF) stimulates the tyrosine kinase activity of the receptor encoded by the protooncogene c-MET. Oncogene. 1991;6:501–4.

    Google Scholar 

  24. Momparler RL. Epigenetic therapy of cancer with 5-aza-2′-deoxycytidine (decitabine). Semin Oncol. 2005;32:443–51.

    Article  CAS  PubMed  Google Scholar 

  25. Png KJ, Yoshida M, Zhang XH, et al. MicroRNA-335 inhibits tumor reinitiation and is silenced through genetic and epigenetic mechanisms in human breast cancer. Genes Dev. 2011;25:226–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Tuck AB, Park M, Sterns EE, Boag A, Elliott BE. Coexpression of hepatocyte growth factor and receptor (met) in human breast carcinoma. Am J Pathol. 1996;148:225–32.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Beviglia L, Matsumoto K, Lin CS, Ziober BL, Kramer RH. Expression of the c-met/HGF receptor in human breast carcinoma: correlation with tumor progression. Int J Cancer. 1997;74:301–9.

    Article  CAS  PubMed  Google Scholar 

  28. Gherardi E, Stoker M. Hepatocyte and scatter factor. Nature. 1990;346:228.

    Article  CAS  PubMed  Google Scholar 

  29. Peruzzi B, Bottaro DP. Targeting the c-Met signaling pathway in cancer. Clin Cancer Res. 2006;12:3657–60.

    Article  CAS  PubMed  Google Scholar 

  30. Garcia S, Dales JP, Charafe-Jauffret E, et al. Poor prognosis in breast carcinomas correlates with increased expression of targetable CD146 and c-Met and with proteomic basal-like phenotype. Hum Pathol. 2007;38:830–41.

    Article  CAS  PubMed  Google Scholar 

  31. Jiang WG, Grimshaw D, Lane J, et al. A hammerhead ribozyme suppresses expression of hepatocyte growth factor/scatter factor receptor c- MET and reduces migration and invasiveness of breast cancer cells. Clin Cancer Res. 2001;7:2555–62.

    CAS  PubMed  Google Scholar 

  32. Cecchi F, Rabe DC, Bottaro DP. Targeting the HGF/c-MET signalling pathway in cancer. Eur J Cancer. 2010;46:1260–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

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

Conflicts of interest

None

Author information

Authors and Affiliations

  1. Molecular Medicine & Cancer Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing, 400016, China

    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

  2. Department of Biochemistry & Molecular Biology, College of Basic Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China

    Fang-zhou Song

Authors
  1. Yue Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fan Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jia-Yan Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hai-Yu Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jian-Jun Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Li Mai
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ji Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Dong-Mei Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yun Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Fang-zhou Song
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fang-zhou Song.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gao, Y., Zeng, F., Wu, JY. et al. MiR-335 inhibits migration of breast cancer cells through targeting oncoprotein c-Met. Tumor Biol. 36, 2875–2883 (2015). https://doi.org/10.1007/s13277-014-2917-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-014-2917-6

Keywords

Search

Navigation