MicroRNA-708 represses hepatic stellate cells activation and proliferation by targeting ZEB1 through Wnt/β-catenin pathway

Eur J Pharmacol. 2020 Mar 15;871:172927. doi: 10.1016/j.ejphar.2020.172927. Epub 2020 Jan 18.

Abstract

Liver fibrosis is caused by a sustained wound healing response to chronic liver injury, and the activation of insubstantial hepatic stellate cells (HSCs) is the key process involved. The progression of liver fibrosis may be attenuated by suppressing activation and proliferation of the HSCs. MicroRNA (miRNA) have emerged as major players in governing fundamental biological processes through multiple mechanisms MiR-708 is known to inhibit the development of hepatocellular carcinoma. However, whether miR-708 can function as a transcriptional regulator in liver fibrosis remains unclear. Our study demonstrated that miR-708 expression was inhibited in fibrotic liver tissues and in activated HSCs, accompanied by an increase of the Zinc finger E-box binding homeobox 1 (ZEB1) level. Besides, overexpression of miR-708 and silencing of ZEB1 inhibited the activation and proliferation of LX-2 cells. While knockdown of miR-708 or overexpression of ZEB1 showed reversed results. Further, dual luciferase reporter assays showed that miR-708 directly targeted ZEB1 in vitro. Interestingly, ZEB1 was found to be involved in HSCs by regulating Wnt/β-catenin signaling pathway. Together, our data showed that miR-708 may be a potential therapeutic target in liver fibrosis therapy.

Keywords: Hepatic stellate cells; MiR-708; MicroRNA; ZEB1; liver fibrosis.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Cell Line
  • Cell Proliferation / genetics
  • Down-Regulation
  • Hepatic Stellate Cells / cytology*
  • Hepatic Stellate Cells / metabolism
  • Hepatic Stellate Cells / pathology
  • Humans
  • Liver Cirrhosis / genetics
  • Male
  • Mice
  • MicroRNAs / genetics*
  • Wnt Signaling Pathway / genetics*
  • Zinc Finger E-box-Binding Homeobox 1 / metabolism*

Substances

  • 3' Untranslated Regions
  • MIRN708 microRNA, human
  • MicroRNAs
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1