HuR-regulated lncRNA NEAT1 stability in tumorigenesis and progression of ovarian cancer

Cancer Med. 2016 Jul;5(7):1588-98. doi: 10.1002/cam4.710. Epub 2016 Apr 14.

Abstract

Long noncoding RNAs (lncRNAs) have recently emerged as pivotal regulators in governing fundamental biological processes, as well as in tumorigenesis. The nuclear paraspeckle assembly transcript 1 (NEAT1) is one of the most highly regulated lncRNAs in recent genomic datasets, however, its biological role and regulatory mechanism in ovarian cancer (OC) development and progression are poorly defined. In this study, we identified that NEAT1 was up-regulated in OC patients and cell lines, and its expression was associated with the FIGO stage and lymph node metastasis. Furthermore, the ectopic expression of NEAT1_1 in OVCAR-3 cell lines promoted cell proliferation and invasion, whereas knockdown of NEAT1_1 did the opposite. Furthermore, NEAT1_1 was stabilized by an RNA-binding protein HuR, but suppressed by miR-124-3p in OC cells. Accordingly, the increased HuR mRNA and decreased miR-124-3p levels were observed in OC patients. These results suggested that lncRNA NEAT1, whose expression was collaboratively controlled by HuR and miR-124-3p, could regulate ovarian carcinogenesis and may serve as a potential target for antineoplastic therapies.

Keywords: HuR; NEAT1; lncRNA; miR-124; ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / metabolism*
  • Disease Progression
  • ELAV-Like Protein 1 / metabolism*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MicroRNAs / genetics
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Protein Binding
  • RNA Interference
  • RNA Stability
  • RNA, Long Noncoding / genetics*

Substances

  • ELAV-Like Protein 1
  • ELAVL1 protein, human
  • MIRN124 microRNA, human
  • MicroRNAs
  • NEAT1 long non-coding RNA, human
  • RNA, Long Noncoding