Up-regulation of microRNA-30b/30d cluster represses hepatocyte apoptosis in mice with fulminant hepatic failure by inhibiting CEACAM1

IUBMB Life. 2020 Jul;72(7):1349-1363. doi: 10.1002/iub.2256. Epub 2020 Feb 26.

Abstract

Recently, impacts of microRNAs have been unraveled in human diseases, and we aimed to confirm the role of miR-30b/30d in fulminant hepatic failure (FHF). Expression of miR-30b/30d and CEACAM1 in serum of FHF patients and healthy people was measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. Mice FHF models were established by injection of D-Galn and lipopolysaccharide, and were treated with miR-30b/30d mimics. Oxidative stress, liver injury, and inflammatory reaction in mouse liver tissues were measured using oxidative stress-related factor kits, hematoxylin-eosin staining and enzyme-linked immunosorbent assay, respectively. Moreover, cell cycle distribution and apoptosis of hepatocytes of mice were determined by flow cytometry, and the target relation between miR-30b/30d and CEACAM1 was confirmed by bioinformatic method and dual luciferase reporter gene assay. MiR-30b/30d expression was positively, and CEACAM1 expression was negatively related to prognosis of FHF patients. Up-regulation of miR-30b/30d attenuated oxidative stress, liver injury, and inflammatory reaction, and improved survival rate of FHF mice. Furthermore, elevated miR-30b/30d ameliorated apoptosis and cell cycle arrest of hepatocytes of FHF mice. CEACAM1 was a target gene of miR-30b/30d. This study highlights that up-regulated miR-30b/30d attenuates the progression of FHF by targeting CEACAM1, which may be helpful to FHF treatment.

Keywords: MicroRNA-30b; MicroRNA-30d; apoptosis; carcinoembryonic antigen-related cell adhesion molecule 1; fulminant hepatic failure.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Antigens, CD
  • Apoptosis*
  • Cell Adhesion Molecules / antagonists & inhibitors*
  • Child
  • Disease Models, Animal*
  • Female
  • Hepatocytes / metabolism*
  • Hepatocytes / pathology
  • Humans
  • Liver Failure, Acute / genetics
  • Liver Failure, Acute / metabolism
  • Liver Failure, Acute / pathology
  • Liver Failure, Acute / prevention & control*
  • Male
  • Mice
  • MicroRNAs / genetics*
  • Middle Aged
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Signal Transduction
  • Up-Regulation
  • Young Adult

Substances

  • Antigens, CD
  • CD66 antigens
  • Cell Adhesion Molecules
  • MIRN30b microRNA, human
  • MIRN30d microRNA, human
  • MicroRNAs
  • NF-kappa B