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

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.

Potential of long non‐coding RNAs in cancer patients: From biomarkers to therapeutic targets

“…For example, decreased expression of ncRuPAR significantly correlates with tumor invasion depth, lymph node metastasis, distant metastasis, tumor size and TNM stage in gastric cancer. 95 A downregulation in the expression of AI364715, 96 GACAT1, 97 and GACAT2 98 in gastric cancer tissues; PCAT29 in prostate cancer 99 ; AC026166.2-001 and RP11-169D4.1-001 in larynx squamous cell carcinoma 100 ; lncRNA-LET 101 and MEG3 86 in GBC tissues could also be used as a prognostic marker. The epigenetic changes in lncRNAs could also predict prognosis of the disease.…”

LncRNAs: Emerging Biomarkers in Gastric Cancer

“…LncRNAs which play tumor-suppressorlike roles were found successively, such as FER1L4 [54], ncRuPAR [57], uc001lsz [49] and MEG3 [56]. They downregulated in GC tissues compared with paired normal tissues and their downregulations were associated with larger tumor size, advanced pathologic stage, more vessel or nerve invasion, more lymphatic and distant metastasis or poorer disease-free survival and overall survival.…”

“…Perineural invasion (tissue level), invasion and lymphatic metastasis (plasma level) [55] MEG3 Tissue Down Tumor size, invasion depth, TNM stage and poor prognosis [56] ncRuPAR Tissue Down Tumor size, invasion depth, lymph node metastasis, distant metastasis and TNM stage [57] BM742401 Tissue Down Poor survival [18,49] DFS: Disease-free survival; OS: Overall survival. 10.…”

Long noncoding RNAs: Novel insights into gastric cancer

“…The diagnostic ability of ncRuPAR to differentiate GC from benign disease was further investigated based on the ROC curve analysis. The optimal cutoff value was 4.97, and AUC was up to 0.84 [24].…”

“…Many novel studies demonstrated that AC096655.1-002 (also named gastric cancer-associated transcript 1 (GACAT1)), ncRuPAR, AA174084, FER1L4, GAS5, GACAT2 and AC138128.1 were significantly down-regulated in GC tissues [24,[28][29][30]32,37,101], while GACAT3, LINC00152, HULC, SUMO1P3, ABHD11-AS1, HOTAIR, PVT1, and GAPLINC were substantially up-regulated in GC tissues [21,25,26,31,35,36,61,102].…”