HIF-2α activated lncRNA NEAT1 promotes hepatocellular carcinoma cell invasion and metastasis by affecting the epithelial-mesenchymal transition

J Cell Biochem. 2018 Apr;119(4):3247-3256. doi: 10.1002/jcb.26481. Epub 2017 Dec 26.

Abstract

The aim of this study was to investigate the role of NEAT1 in hepatocellular carcinoma (HCC), and probe whether NEAT1 participate in the epithelial-mesenchymal transition (EMT) and metastasis regulated by HIF-2α. Expression of lncRNA NEAT1 was initially assessed in HCC tissues and in a series of HCC cell lines. The correlations between NEAT1 levels and HIF-2α were analyzed through plasmid vector construction. The potential underlying mechanisms of NEAT1 in HCC were performed through in vitro and in vivo functional assays. Expression of NEAT1, HIF-2α were significantly increased in HCC tissues and cell lines. Then, in vitro assays revealed that NEAT1 promotes EMT and metastasis by stimulating the inactivation of HIF-2α in HCC. An in vivo animal model also demonstrated the cancer promotion mechanism of NEAT1. In this study, we found that the NEAT1 was high expression in HCC. NEAT1 promotes tumor cell EMT, migration and invasion capacities by stimulating the activation of HIF-2α in HCC.

Keywords: HIF-2α; NEAT1; epithelial-mesenchymal transition (EMT); hepatocellular carcinoma (HCC); metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition
  • Gene Expression Regulation, Neoplastic
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology*
  • Mice
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • Up-Regulation*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • NEAT1 long non-coding RNA, human
  • RNA, Long Noncoding
  • endothelial PAS domain-containing protein 1