Skip to main content

Advertisement

Log in

The expression of heparanase and microRNA-1258 in human non-small cell lung cancer

  • Research Article
  • Published:
Tumor Biology

Abstract

This study aims to discuss the correlation between miR-1258 and the expression of heparanase (HPSE) in the cancer cells of the patients with non-small cell lung cancer (NSCLC) and the inhibition mechanism of miR-1258 on the invasion of lung cancer cell. The expression level of miR-1258 was detected by TaqMan real-time PCR assay, the expression of HPSE was detected by immunohistochemistry, and the expression level of HPSE in the cancer tissue of each case was detected by western blot and in its adjacent tissue of 53 patients with NSCLC. The influence of miR-1258 on the invasion potential of the lung cancer cell line A549 was studied with lentivirus system including cloned miR-1258 fragments subsequently. The expression of HPSE and miR-1258 in NSCLC tissue was not obviously related to patient’s gender, age, differentiation extent of cancer tissue, cancer types, etc., but also staging and lymph node metastasis, and the difference was significant. Further studies showed that the relationship between the expression level of miR-1258 and the expression of HPSE was closer. The relative expression level of miR-1258 was 0.58 ± 0.07 in HPSE positive sample and 1.58 ± 0.11 in HPSE negative sample, and the difference of which was notably significant (P < 0.0001). Western blot showed that the expression level of HPSE was highly negatively related to the expression level of miR-1258. The invasion potential of A549 was notably lowered when transfected by miR-1258. The miR-1258 regulates the expression level of HPSE to influence the morbidity and metastasis of NSCLC. The miR-1258 is likely to become the key to the treatment of lung cancer metastasis.

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

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Höök M, Wasteson Å, Oldberg Å. A heparin sulfate-degrading endoglycosidase from rat liver tissue. Biochem Biophys Res Commun. 1975;67(4):1422–8

    Google Scholar 

  2. Hulett MD, Freeman C, Hamdori BJ, et al. Cloning of mammalian heparanase: an important enzyme in tumor invasion and metastasis. J Nat Med. 1999;5(7):803–9.

    Article  CAS  Google Scholar 

  3. Vlodavsky I, Friedmann Y, Elkin M, et al. Mammalian heparanase: gene cloning, expression and function in tumor progression and metastasis. Nat Med. 1999;5(7):793–802.

    Article  CAS  PubMed  Google Scholar 

  4. Ilan N, Elkin M, Vlodavsky I. Regulation, function, and clinical significance of heparanase in cancer metastasis and angiogenesis. Int J Biochem Cell Biol. 2006;38:2018–39.

    Article  CAS  PubMed  Google Scholar 

  5. Zcharia E, Jia J, Zhang S, Baraz L, Lindahl U, Peretz T, et al. Newly generated heparanase knock-out mice unravel co-regulation of heparanase and matrix metalloproteinases. PLoS One. 2008;4:e5181.

    Article  Google Scholar 

  6. Edovitsky E, Elkin M, Zcharia E, Peretz T, Vlodavsky I. Heparanase gene silencing, tumor invasiveness, angiogenesis, and metastasis. J Natl Cancer Inst. 2004;96:1219–30.

    Article  CAS  PubMed  Google Scholar 

  7. Chen CZ. MicroRNAs as oncogenes and tumor suppressors. New Engl J Med. 2005;353:1768–71.

    Article  CAS  PubMed  Google Scholar 

  8. Tavazoie SF, Alarco 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 

  9. Valastyan S, Reinhardt F, Benaich N, Calogrias D, Richardson A, Weinberg RA. A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis. Cell. 2009;137:1032–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Sachdeva M, Mo YY. MicroRNA-145 suppresses cell invasion and metastasis by directly targeting mucin 1. Cancer Res. 2010;70:378–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Creighton CJ, Fountain MD, Yu Z, Nagaraja AK, Zhu H, Khan M, et al. Molecular profiling uncovers a p53-associated role for microRNA-31 in inhibiting the proliferation of serous ovarian carcinomas and other cancers. Cancer Res. 2010;70:1906–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Zhang L, Sullivan PS, Goodman JC, et al. MicroRNA-1258 suppresses breast cancer brain metastasis by targeting heparanase. Cancer Res. 2011;71:645–54. Published OnlineFirst February 1, 2011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Sajnani-Perez G, Chilton JK, Aricescu AR, et al. Isoform-specific binding of the tyrosine phosphatase PTP sigma to a ligand in developing muscle. Mol Cell Neurosci. 2003;22(1):37–48.

    Article  CAS  PubMed  Google Scholar 

  14. Okawa T, Naomoto Y, Nobuhisa T, et al. Heparanase is involved in angiogenesis in esophageal cancer through induction of cyclooxygenase-2. Clin Cancer Res. 2005;11(22):7995–8005.

    Article  CAS  PubMed  Google Scholar 

  15. Sommerfeldt N, Beckhove P. Heparanase: a new metastasis-associated antigen recognized in breast cancer patients by spontaneously induced memory T lymphocytes. Cancer Res. 2006;66(15):7716–23.

    Article  CAS  PubMed  Google Scholar 

  16. Xie ZJ, Liu Y, Jia LM, et al. Heparanase expression, degradation of basement membrane and low degree of infiltration by immunocytes correlate with invasion and progression of human gastric cancer. World J Gastroenterol. 2008;14(24):3812–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Quiros RM, Rao G, Plate J, et al. Elevated serum heparanase-1 levels in patients with pancreatic carcinoma are associated with poor survival. Cancer. 2006;106(3):532–40.

    Article  CAS  PubMed  Google Scholar 

  18. Shafat I, Pode D, Peretz T, et al. Clinical significance of urine heparanase in bladder cancer progression. Neoplasia. 2008;10(2):125–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This study was supported by a grant from Shanghai Natural Science Fund of China (09ZR1425900).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gening Jiang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liu, H., Chen, X., Gao, W. et al. The expression of heparanase and microRNA-1258 in human non-small cell lung cancer. Tumor Biol. 33, 1327–1334 (2012). https://doi.org/10.1007/s13277-012-0380-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-012-0380-9

Keywords