miRNA-150-5p promotes hepatic stellate cell proliferation and sensitizes hepatocyte apoptosis during liver fibrosis

Epigenomics. 2020 Jan;12(1):53-67. doi: 10.2217/epi-2019-0104. Epub 2019 Dec 13.

Abstract

Aim: To explore the role of miRNA-150-5p (miR-150-5p) in liver fibrosis. Materials & methods: miRNA expression profiles, CCl4-induced liver fibrosis progression and regression rodent models, quantitative real-time PCR, miR-150-5p mimics and inhibitors, cell proliferation and apoptosis detection, RNA sequencing and bioinformatics analysis were employed. Results: Liver tissue miR-150-5p expression was positively associated with liver fibrosis progression and regression; however, miR-150-5p exhibited a cell-specific expression pattern, namely, it was enhanced in hepatocytes but reduced in hepatic stellate cells (HSCs) during liver fibrosis; miR-150-5p overexpression promoted HSC apoptosis and sensitized hepatocyte apoptosis; miR-150-5p mimic had a larger influence on the transcriptomic stability of HSCs than that of hepatocytes; miR-150-5p mediated activation of interferon signaling pathways might be responsible for HSC apoptosis. Conclusion: miR-150-5p exhibited an opposite regulation and function pattern between HSCs and hepatocytes during liver fibrosis.

Keywords: apoptosis; cell specific; hepatic stellate cell; hepatocyte; liver fibrosis; miR-150-5p; proliferation; transcriptome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics*
  • Biomarkers
  • Disease Susceptibility
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Hepatic Stellate Cells / metabolism*
  • Hepatocytes / metabolism*
  • Humans
  • Liver Cirrhosis / etiology*
  • Liver Cirrhosis / metabolism
  • MicroRNAs / genetics*
  • RNA Interference*
  • Signal Transduction
  • Transcriptome

Substances

  • Biomarkers
  • MIRN150 microRNA, human
  • MicroRNAs