MiR-429 regulates rat liver regeneration and hepatocyte proliferation by targeting JUN/MYC/BCL2/CCND1 signaling pathway

Cell Signal. 2018 Oct:50:80-89. doi: 10.1016/j.cellsig.2018.06.013. Epub 2018 Jun 26.


Increasing evidence indicates that miR-429 is involved in tumor suppression in various human cancers. However, its role in liver regeneration remains unexplored. Liver regeneration is a highly orchestrated process that can be regulated by microRNAs (miRNAs), although the mechanisms are largely unclear. In this study, we aimed to identify the role of miR-429 in hepatocyte proliferation during liver regeneration. First, we performed microarray analysis and qRT-PCR. Results indicated that miR-429 level in rat liver markedly decreased 30 h after partial hepatectomy, and miR-429 overexpression disrupted BRL-3A proliferation and the transition of G1 to S phase in rat hepatocyte and promoted hepatocyte apoptosis. By contrast, miR-429 down-regulation had inverse effects. MiR-429 negatively regulated JUN expression in vitro and in vivo. After using JUN siRNA, we found that JUN inhibition mediates the effect of miR-429 in hepatocyte proliferation and growth and miR-429 negatively regulates JUN/MYC/BCL2/CCND1 signaling pathways. Our results also indicated that miR-429 inhibits hepatocyte proliferation and liver regeneration by targeting JUN/MYC/BCL2/CCND1.

Keywords: Hepatocyte; JUN; Liver regeneration; MiR-429; Proliferation.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Line
  • Cell Proliferation / genetics*
  • Cyclin D1 / genetics
  • Down-Regulation / genetics
  • Hepatectomy / methods
  • Hepatocytes / physiology*
  • Liver / physiology
  • Male
  • MicroRNAs / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-jun / genetics
  • Proto-Oncogene Proteins c-myc / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / genetics*


  • MIRN429 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-jun
  • Proto-Oncogene Proteins c-myc
  • Cyclin D1