MiR-199a-5p regulates rat liver regeneration and hepatocyte proliferation by targeting TNF-α TNFR1/TRADD/CASPASE8/CASPASE3 signalling pathway

Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):4110-4118. doi: 10.1080/21691401.2019.1683566.

Abstract

Abnormally expressed miR-199a-5p (miR-199a) has been frequently reported in multiple types of malignancies. Nevertheless, its effect in liver regeneration (LR) is largely still unclear. Herein, we investigated the function of miR-199a in hepatocyte proliferation during LR. As a result, miR-199a expression was significantly increased 12-30 h, in rat hepatic tissue, after partial hepatectomy (PH). The down-regulated expression of miR-199a inhibited proliferation as well as promoted cell apoptosis of BRL-3A. Additionally, TNF-α was found as a target of miR-199a. The administration of TNF-α siRNA regulated the effects of miR-199a on hepatocyte proliferation as well as miR-199a-modulated TNF-α/TNFR1/TRADD/CASPASE8/CASPASE3 signalling pathways. Taken together, these present findings suggested that miR-199a promoted hepatocyte proliferation as well as LR via targeting TNF-α/TNFR1/TRADD/CASPASE8/CASPASE3.

Keywords: MiR-199a; TNF-α; hepatocyte; liver regeneration; proliferation.

MeSH terms

  • Animals
  • Caspase 3 / metabolism
  • Caspase 8 / metabolism
  • Cell Proliferation / genetics
  • Hepatocytes / cytology*
  • Liver Regeneration / genetics*
  • MicroRNAs / genetics*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Tumor Necrosis Factor, Type I / metabolism
  • Signal Transduction / genetics*
  • TNF Receptor-Associated Death Domain Protein / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation / genetics

Substances

  • MIRN199 microRNA, rat
  • MicroRNAs
  • Receptors, Tumor Necrosis Factor, Type I
  • TNF Receptor-Associated Death Domain Protein
  • Tumor Necrosis Factor-alpha
  • Caspase 3
  • Caspase 8