Long non-coding RNA F11-AS1 inhibits HBV-related hepatocellular carcinoma progression by regulating NR1I3 via binding to microRNA-211-5p

J Cell Mol Med. 2020 Jan;24(2):1848-1865. doi: 10.1111/jcmm.14881. Epub 2019 Dec 27.

Abstract

Long non-coding RNAs (lncRNAs) could regulate growth and metastasis of hepatocellular carcinoma (HCC). In this study, we aimed to investigate the mechanism of lncRNA F11-AS1 in hepatitis B virus (HBV)-related HCC. The relation of lncRNA F11-AS1 expression in HBV-related HCC tissues to prognosis was analysed in silico. Stably HBV-expressing HepG2.2.15 cells were established to explore the regulation of lncRNA F11-AS1 by HBx protein, as well as to study the effects of overexpressed lncRNA F11-AS1 on proliferation, migration, invasion and apoptosis in vitro. Subsequently, the underlying interactions and roles of lncRNA F11-AS1/miR-211-5p/NR1I3 axis in HBV-related HCC were investigated. Additionally, the influence of lncRNA F11-AS1 and miR-211-5p on tumour growth and metastasis capacity of HepG2.2.15 cells were studied on tumour-bearing nude mice. Poor expression of lncRNA F11-AS1 was correlated with poor prognosis in patients with HBV-related HCC, and its down-regulation was caused by the HBx protein. lncRNA F11-AS1 was proved to up-regulate the NR1I3 expression by binding to miR-211-5p. Overexpression of lncRNA F11-AS1 reduced the proliferation, migration and invasion, yet induced apoptosis of HepG2.2.15 cells in vitro, which could be abolished by overexpression of miR-211-5p. Additionally, either lncRNA F11-AS1 overexpression or miR-211-5p inhibition attenuated the tumour growth and metastasis capacity of HepG2.2.15 cells in vivo. Collectively, lncRNA F11-AS1 acted as a modulator of miR-211-5p to positively regulate the expression of NR1I3, and the lncRNA F11-AS1/miR-211-5p/NR1I3 axis participated in HBV-related HCC progression via interference with the cellular physiology of HCC.

Keywords: hepatitis B virus; hepatocellular carcinoma; long non-coding RNA F11-antisense 1; microRNA-211-5p; nuclear receptor constitutive androstane receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Base Sequence
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / virology*
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Constitutive Androstane Receptor
  • Disease Progression*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Hep G2 Cells
  • Hepatitis B virus / physiology*
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Liver Neoplasms / virology
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Models, Biological
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Prognosis
  • Protein Binding
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Trans-Activators / metabolism
  • Up-Regulation / genetics
  • Viral Regulatory and Accessory Proteins / metabolism

Substances

  • Constitutive Androstane Receptor
  • MIRN211 microRNA, human
  • MicroRNAs
  • NR1I3 protein, human
  • Nr1i3 protein, mouse
  • RNA, Long Noncoding
  • Receptors, Cytoplasmic and Nuclear
  • Trans-Activators
  • Viral Regulatory and Accessory Proteins
  • hepatitis B virus X protein