Skip to main content

Advertisement

Log in

ncRuPAR inhibits gastric cancer progression by down-regulating protease-activated receptor-1

  • Research Article
  • Published:
Tumor Biology

Abstract

ncRuPAR is a newly discovered long noncoding RNA molecule that can upregulate protease-activated receptor-1 (PAR-1) during embryonic growth; however, its role in cancer has not been elucidated. Here, we conducted a study to investigate the role of ncRuPAR in gastric cancer. Significant downregulation of ncRuPAR was detected in gastric cancer tissues compared with paired adjacent nontumor tissues; however, both PAR-1 and vascular endothelial growth factor (VEGF) messenger RNA (mRNA) levels were significantly higher in cancerous tissues compared with adjacent normal tissues. Additionally, the expression level of ncRuPAR was found to be significantly correlated with tumor invasion depth, lymph node metastasis, distant metastasis, tumor size, and tumor-nodes-metastasis (TNM) stage and inversely associated with the mRNA levels and extent (E) × intensity (I) scores of PAR-1 and VEGF. The protein level of PAR-1 was significantly correlated with tumor size only, while the VEGF protein level was significantly correlated with invasion depth and tumor size. The area under the receiver operating characteristic (ROC) curve of ncRuPAR was 0.84 (95 % CI 0.79–0.88) at a cutoff value of 4.97; ncRuPAR had a sensitivity of 88.41 %, a specificity of 73.91 %, and an accuracy of 81.16 % for the prediction of gastric cancer. These results suggest that ncRuPAR inhibits gastric cancer development, and its underlying mechanism involves the inhibition of PAR-1. In addition, ncRuPAR could be regarded as a marker for gastric cancer in the future.

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

Access this article

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

Similar content being viewed by others

References

  1. Brenner H, Rothenbacher D, Arndt V. Epidemiology of stomach cancer. Methods Mol Biol. 2009;472:467–77.

    Article  PubMed  Google Scholar 

  2. Zhu Y, Xiao X, Dong L, et al. Investigation and identification of let-7a related functional proteins in gastric carcinoma by proteomics. Anal Cell Pathol (Amst). 2012;35(4):285–95.

    CAS  Google Scholar 

  3. Zhai XF, Chen Z, Li B, et al. Traditional herbal medicine in preventing recurrence after resection of small hepatocellular carcinoma: a multicenter randomized controlled trial. J Integr Med. 2013;11:90–100.

    Article  PubMed  Google Scholar 

  4. Sun DZ, Liu L, Jiao JP, et al. Syndrome characteristics of traditional Chinese medicine: summary of a clinical survey in 767 patients with gastric cancer. J Chinese Integr Med. 2010;8(4):332–40.

    Article  Google Scholar 

  5. Wang WJ. Enhancing the treatment of metabolic syndrome with integrative medicine. J Integr Med. 2013;11(3):153–6.

    Article  PubMed  Google Scholar 

  6. Liu D, Zhang Z, Kong CZ. High FOXM1 expression was associated with bladder carcinogenesis. Tumor Biol. 2013;34:1131–8.

    Article  CAS  Google Scholar 

  7. Hu BS, Hu H, Zhu CY, et al. Overexpression of GOLPH3 is associated with poor clinical outcome in gastric cancer. Tumor Biol. 2013;34(1):515–20.

    Article  Google Scholar 

  8. Yang F, Bi JW, Xue XC, et al. Upregulated long non-coding RNA H19 contributes to proliferation of gastric cancer cells. FEBS J. 2012;279(17):3159–65.

    Article  CAS  PubMed  Google Scholar 

  9. Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell. 2009;136(4):629–41.

    Article  CAS  PubMed  Google Scholar 

  10. Muers M. RNA: genome-wide views of long non-coding RNAs. Nat Rev Genet. 2011;12(11):742.

    Article  CAS  PubMed  Google Scholar 

  11. Huarte M, Guttman M, Feldser D, et al. A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell. 2010;142(3):409–19.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Gupta RA, Shah N, Wang KC, et al. Long noncoding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464(7291):1071–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Panzitt K, Tschernatsch MM, Guelly C, et al. Characterization of HULC, a novel gene with striking up-regulation in hepatocellular carcinoma, as noncoding RNA. Gastroenterology. 2007;132(1):330–42.

    Article  CAS  PubMed  Google Scholar 

  14. Wang KC, Chang HY. Molecular mechanisms of long noncoding RNAs. Mol Cell. 2011;43(6):904–14.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Tsai MC, Spitale RC, Chang HY. Long intergenic noncoding RNAs: new links in cancer progression. Cancer Res. 2011;71(1):3–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Yan B, Wang Z. Long noncoding RNA. Its physiological and pathological roles. DNA Cell Biol. 2012;31 Suppl 1:S34–41.

    PubMed  Google Scholar 

  17. Madamanchi NR, Hu ZY, Li F, et al. A noncoding RNA regulates human protease-activated receptor-1 gene during embryogenesis. Biochim Biophys Acta. 2002;1576(3):237–45.

    Article  CAS  PubMed  Google Scholar 

  18. Trotti A, Fritz AG, Compton CC, et al. AJCC cancer staging manual. 7th ed. New York: Springer; 2009. p. 117–26.

    Google Scholar 

  19. Sarela AI, Verbeke CS, Ramsdale J, et al. Expression of survivin, a novel inhibitor of apoptosis and cell cycle regulatory protein, in pancreatic adenocarcinoma. Br J Cancer. 2002;86:886–92.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Barbareschi M, Maisonneuve P, Aldovini D, et al. High syndecan-1 expression in breast carcinoma is related to an aggressive phenotype and to poorer prognosis. Cancer. 2003;98(3):474–83.

    Article  PubMed  Google Scholar 

  21. Lee SR, Kim HO, Shin JH, et al. Prognostic significance of quantitative carcinoembryonic antigen and cytokeratin 20 mRNA detection in peritoneal washes of gastric cancer patients. Hepatogastroenterology. 2013;60(125):1237–44.

    CAS  PubMed  Google Scholar 

  22. Yoshimizu T, Miroglio A, Ripoche MA, et al. The H19 locus acts in vivo as a tumor suppressor. Proc Natl Acad Sci U S A. 2008;105(34):12417–22.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Matouk IJ, DeGroot N, Mezan S, et al. The H19 non-coding RNA is essential for human tumor growth. PLoS One. 2007;2(9):e845.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature. 2000;407(6801):249–57.

    Article  CAS  PubMed  Google Scholar 

  25. Folkman J. Tumor angiogenic therapeutic implications. N Engl J Med. 1971;285(21):1182–6.

    Article  CAS  PubMed  Google Scholar 

  26. Coughlin SR. Thrombin signalling and protease-activated receptors. Nature. 2000;407(6801):258–64.

    Article  CAS  PubMed  Google Scholar 

  27. Dorsam RT, Gutkind JS. G-protein-coupled receptors and cancer. Nat Rev Cancer. 2007;7(2):79–94.

    Article  CAS  PubMed  Google Scholar 

  28. Even-Ram S, Uziely B, Cohen P, et al. Thrombin receptor overexpression in malignant and physiological invasion processes. Nat Med. 1998;4(8):909–14.

    Article  CAS  PubMed  Google Scholar 

  29. Darmoul D, Gratio V, Devaud H, et al. Aberrant expression and activation of the thrombin receptor protease-activated receptor-1 induces cell proliferation and motility in human colon cancer cells. Am J Pathol. 2003;162(5):1503–13.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Daaka Y. G proteins in cancer: the prostate cancer paradigm. Sci STKE. 2004;2004(216):re2.

    PubMed  Google Scholar 

  31. Vu TK, Hung DT, Wheaton VI, et al. Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell. 1991;64(6):1057–68.

    Article  CAS  PubMed  Google Scholar 

  32. Yin YJ, Salah Z, Maoz M, et al. Oncogenic transformation induces tumor angiogenesis: a role for PAR1 activation. FASEB J. 2003;17(2):163–74.

    Article  CAS  PubMed  Google Scholar 

  33. Mei DY, Song HJ, Wang K, et al. Up-regulation of SUMO1 pseudogene 3 (SUMO1P3) in gastric cancer and its clinical association. Med Oncol. 2013;30(4):709.

    Article  PubMed  Google Scholar 

  34. Mohammadreza H, Mehrdad B, Majid S, et al. Up-regulation of HOTAIR long non-coding RNA in human gastric adenocarcinoma tissues. Med Oncol. 2013;30(3):670.

    Article  Google Scholar 

  35. Sun WL, Wu YB, Yu X, et al. Decreased expression of long noncoding RNA AC096655.1-002 in gastric cancer and its clinical significance. Tumor Biol. 2013;34(5):2697–701.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China (grants 81102693 and 81102565).

Conflicts of interest

None

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Xiaoqiang Yue.

Additional information

Long Liu, Bing Yan, and Zhihui Yan contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, L., Yan, B., Yang, Z. et al. ncRuPAR inhibits gastric cancer progression by down-regulating protease-activated receptor-1. Tumor Biol. 35, 7821–7829 (2014). https://doi.org/10.1007/s13277-014-2042-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-014-2042-6

Keywords

Navigation