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

Tumour Biol. 2014 Aug;35(8):7821-9. doi: 10.1007/s13277-014-2042-6. Epub 2014 May 12.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Disease Progression
  • Female
  • Humans
  • Male
  • Middle Aged
  • RNA, Long Noncoding / physiology*
  • ROC Curve
  • Receptor, PAR-1 / antagonists & inhibitors
  • Receptor, PAR-1 / genetics*
  • Stomach Neoplasms / pathology*
  • Vascular Endothelial Growth Factor A / analysis
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • RNA, Long Noncoding
  • Receptor, PAR-1
  • Vascular Endothelial Growth Factor A