Decreased expression of the long non-coding RNA FENDRR is associated with poor prognosis in gastric cancer and FENDRR regulates gastric cancer cell metastasis by affecting fibronectin1 expression

J Hematol Oncol. 2014 Aug 29;7:63. doi: 10.1186/s13045-014-0063-7.

Abstract

Background: FENDRR is a long non-coding RNAs (lncRNA) that binds to polycomb repressive complexe 2 (PRC2) to epigenetically regulate the expression of its target gene. The clinical role of FENDRR in carcinomas remains yet to be found.

Method: Real-time polymerase chain reaction (PCR) was used to examine FENDRR expression in gastric cancer cell lines/tissues compared with normal epithelial cells/adjacent non-tumorous tissues. Cell proliferation assays, Wound healing assays, and in vitro and in vivo invasion and migration assays were performed to detect the biological effects of FENDRR in gastric cancer cells. Real-time PCR, western-blot and immunohistochemistry were used to evaluate the mRNA and protein expression of fibronectin1 (FN1). Secreted matrix metalloproteinase (MMP) activities were detected and characterized using gelatin zymography assay.

Results: FENDRR was downregulated in gastric cancer cell lines and cancerous tissues, as compared with normal gastric epithelial cells and adjacent noncancerous tissue samples. Low FENDRR expression was correlated with deeper tumor invasion (p < 0.001), higher tumor stage (p = 0.001), and lymphatic metastasis (p = 0.007). Univariate and multivariate analyses indicated that low FENDRR expression predicted poor prognosis. Histone deacetylation was involved in the downregulation of FENDRR in gastric cancer cells. FENDER overexpression suppressed invasion and migration by gastric cancer cells in vitro, by downregulating FN1 and MMP2/MMP9 expression.

Conclusion: Low expression of the lncRNA FENDRR occurs in gastric cancer and is associated with poor prognosis. Thus, FENDRR plays an important role in the progression and metastasis of gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / mortality
  • Animals
  • Biomarkers, Tumor / genetics*
  • Blotting, Western
  • Cell Line, Tumor
  • Disease-Free Survival
  • Fibronectins / biosynthesis*
  • Gene Expression Regulation, Neoplastic / genetics*
  • Heterografts
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Mice
  • Mice, Nude
  • Neoplasm Metastasis / genetics
  • Prognosis
  • Proportional Hazards Models
  • RNA, Long Noncoding / genetics*
  • Real-Time Polymerase Chain Reaction
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / mortality

Substances

  • Biomarkers, Tumor
  • FN1 protein, human
  • Fibronectins
  • RNA, Long Noncoding