Long noncoding RNA OIP5-AS1 aggravates cell proliferation, migration in gastric cancer by epigenetically silencing NLRP6 expression via binding EZH2

J Cell Biochem. 2020 Jan;121(1):353-362. doi: 10.1002/jcb.29183. Epub 2019 Jun 20.

Abstract

The critical role of long noncoding RNAs (lncRNAs) in the development of multiple cancers has been revealed either functioning as a tumor initiator or a cancer suppressor. A widely recognized OIP5 antisense RNA 1 (lncRNA OIP5-AS1) has been validated to be an essential regulator of the tumorigenesis of various malignancies. Whereas, the potential role and the exact mechanism of lncRNA OIP5-AS1 by which OIP5-AS1 mediates gastric cancer (GC) progression remains vague. Therefore, first our work probed its expression levels in GC cell lines and related normal cells by real-time quantitative polymerase chain reaction. The heightened level of OIP5-AS1 was detected in GC cell lines. In terms of its cellular effects, we performed a series of functional experiments and as presented in the assays, the proliferative potential and motility was diminished. However, more apoptotic cells were induced with the introduction of OIP5-AS1 silencing. Meanwhile, higher Nod-like receptor pyrin domain-containing protein 6 (NLRP6) and enhancer of zeste homolog 2 (EZH2) expression in the GC cells was monitored. Besides, OIP5-AS1 was disclosed to locate mainly in the nucleus. In terms of mechanism, OIP5-AS1 directly bound to EZH2 and obstructed NLRP6 expression, speeding up GC progression.

Keywords: EZH2; NLRP6; OIP5-AS1; gastric cancer.

MeSH terms

  • Apoptosis
  • Cell Movement
  • Cell Nucleus / metabolism
  • Cell Proliferation
  • Disease Progression
  • Enhancer of Zeste Homolog 2 Protein / metabolism*
  • Epigenesis, Genetic
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism

Substances

  • Intracellular Signaling Peptides and Proteins
  • NLRP6 protein, human
  • RNA, Long Noncoding
  • long noncoding RNA OIP5, human
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein