MicroRNA-183 accelerates the proliferation of hepatocyte during liver regeneration through targeting programmed cell death protein 6

Genes Genomics. 2022 Aug;44(8):1017-1029. doi: 10.1007/s13258-022-01223-2. Epub 2022 Feb 21.

Abstract

Background: Liver regeneration is a highly orchestrated process concerning the modulation of various microRNAs (miRs). miR-183 was recently found to be involved in the process of liver regeneration, that miR-183 was remarkably up-regulated at 2-6 h after partial hepatectomy.

Objective: This study was aimed to explore the mechanism of miR-183 in on liver regeneration.

Methods: After partial hepatectomy (PH) or transfection, we measured the changes of miR-183 and programmed cell death protein 6 (PDCD6) levels in rats and the hepatocytes. The histopathology was observed with hematoxylin-eosin staining. The miR-183 mimic and inhibitor plasmids were intravenously injected into rats, and the liver weight/body weight ratio was calculated. The prediction of TargetScan and the validation of luciferase activity assay were employed to confirm the targeting relationship between miR-183 and PDCD6. The viability, apoptosis and cell cycle of transfected rat hepatocyte BRL-3A were determined via MTT and flow cytometry assays.

Results: MiR-183 expression showed a contrary tendency with that of PDCD6 during liver regeneration. Enhanced miR-183 in rats could notably increase liver/body weight ratio, while its inhibition did conversely. Overexpressed PDCD6, a target of miR-183, repressed the viability and cell cycle in hepatocytes, whereas its silence led to contrary results. Overexpressed miR-183 in BRL-3A cells enhanced cell viability and promoted the cell cycle yet suppressed apoptosis, whereas its inhibition showed contrary results, which were offset by PDCD6.

Conclusions: Collectively, miR-183 promoted liver regeneration via targeting PDCD6.

Keywords: Hepatic index; Hepatocytes; Liver regeneration; Partial hepatectomy; microRNA-183.

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins
  • Body Weight
  • Calcium-Binding Proteins / metabolism
  • Cell Proliferation / genetics
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Humans
  • Liver Regeneration* / genetics
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Rats

Substances

  • Apoptosis Regulatory Proteins
  • Calcium-Binding Proteins
  • MIRN183 microRNA, human
  • MIRN183 microRNA, rat
  • MicroRNAs
  • PDCD6 protein, human