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

Chunyan Zhang1, Cuifang Chang2, Hang Gao2

  • 1Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, 830046, China; State Key Laboratory Cultivation Base for Cell Differentiation Regulation and Henan Engineering Laboratory for Bioengineering and Drug Development, College of Life Science, Henan Normal University, Xinxiang 453007, Henan, China.

Cellular Signalling
|July 1, 2018
PubMed

Insights

MicroRNA-429 (miR-429) inhibits liver regeneration by suppressing hepatocyte proliferation. Downregulation of miR-429 promotes liver growth by targeting the JUN/MYC/BCL2/CCND1 pathway.

Area of Science:

  • Molecular Biology
  • Hepatology
  • MicroRNA Research

Background:

  • MicroRNAs (miRNAs) regulate biological processes, including liver regeneration.
  • The specific role of miR-429 in liver regeneration is currently unknown.
  • Previous studies suggest miR-429 acts as a tumor suppressor in various cancers.

Purpose of the Study:

  • To investigate the function of miR-429 in hepatocyte proliferation during liver regeneration.
  • To elucidate the molecular mechanisms underlying miR-429's role in liver regeneration.

Main Methods:

  • Microarray analysis and quantitative real-time PCR (qRT-PCR) to assess miR-429 levels.
  • In vitro and in vivo experiments using rat hepatocytes and liver models.
  • Small interfering RNA (siRNA) targeting JUN to investigate downstream effects.

Main Results:

  • miR-429 levels significantly decreased in rat liver post-partial hepatectomy.
  • Overexpression of miR-429 inhibited hepatocyte proliferation, G1 to S phase transition, and promoted apoptosis.
  • Downregulation of miR-429 demonstrated inverse effects on hepatocyte proliferation.
  • miR-429 was found to negatively regulate JUN expression both in vitro and in vivo.
  • JUN inhibition mediated the effects of miR-429 on hepatocyte proliferation and growth.
  • miR-429 negatively regulates the JUN/MYC/BCL2/CCND1 signaling pathway.

Conclusions:

  • miR-429 plays an inhibitory role in hepatocyte proliferation and liver regeneration.
  • The mechanism involves the negative regulation of the JUN/MYC/BCL2/CCND1 signaling pathway.
  • Targeting miR-429 may offer therapeutic potential for enhancing liver regeneration.
Keywords:
HepatocyteJUNLiver regenerationMiR-429Proliferation

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