The long noncoding RNA PVT1 functions as a competing endogenous RNA by sponging miR-186 in gastric cancer

Biomed Pharmacother. 2017 Apr;88:302-308. doi: 10.1016/j.biopha.2017.01.049. Epub 2017 Feb 24.

Abstract

Background: Recent evidence has highlighted the key regulatory roles of long non-coding RNAs (lncRNAs) in tumor development and progression including gastric cancer (GC).The long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) has been identified as an oncogene in some tumors. However, the potential biological roles and regulatory mechanisms of PVT1 involved in GC remained poorly understood.

Methods: Quantitative real-time PCR (QRT-PCR) was used to determine the expression of PVT1 and miR-186 in GC tissues. The MTT cell proliferation and transwell invasion assays were used to detect the cell proliferation and invasion abilities. Western-blotting analysis was used to detect the protein expression of PCNA and HIF-1α. To understand the tumorigenic mechanism of PVT1, luciferase reporter assays were performed to evaluate whether the miR-186 was a target of PVT1 in GC cells.

Results: In the current study, we showed that PVT1 expression was markedly upregulated in GC tissues and cell lines, and high expression levels of PVT1 were obviously correlated with advanced tumor stage and lymph node metastasis. Further functional experiments indicated up-regulation of PVT1 promoted the GC cell proliferation and invasion, while down-regulation of PVT1 inhibited cell proliferation and invasion. In addition, PVT1 could directly interact with miR-186 in GC cells and this interaction lead to the inhibition of downstream of HIF-1α expression.

Conclusions: These results suggested that PVT1 acted as a key role in GC pathogenesis and may serve as a potential therapeutic target for GC.

Keywords: Cell proliferation; Gastric cancer; Plasmacytoma variant translocation 1; miR-186.

MeSH terms

  • Adult
  • Aged
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Female
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis
  • Lymphatic Metastasis / prevention & control
  • Male
  • MicroRNAs / drug effects*
  • Middle Aged
  • Neoplasm Invasiveness / prevention & control
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / pharmacology*
  • RNA, Neoplasm / drug effects*
  • Stomach Neoplasms / drug therapy*

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit
  • MIRN186 microRNA, human
  • MicroRNAs
  • PVT1 long-non-coding RNA, human
  • RNA, Long Noncoding
  • RNA, Neoplasm