MiR-126 Regulates Properties of SOX9+ Liver Progenitor Cells during Liver Repair by Targeting Hoxb6

Stem Cell Reports. 2020 Sep 8;15(3):706-720. doi: 10.1016/j.stemcr.2020.07.005. Epub 2020 Aug 6.

Abstract

Liver progenitor cells (LPCs) have a remarkable contribution to the hepatocytes and ductal cells when normal hepatocyte proliferation is severely impaired. As a biomarker for LPCs, Sry-box 9 (Sox9) plays critical roles in liver homeostasis and repair in response to injury. However, the regulation mechanism of Sox9 in liver physiological and pathological state remains unknown. In this study, we found that miR-126 positively regulated the expression of Sox9, the proliferation and differentiation of SOX9+ LPCs by suppressing the translation of homeobox b6 (Hoxb6). As a transcription factor, HOXB6 directly binds to the promoter of Sox9 to inhibit Sox9 expression, resulting in the destruction of the properties of SOX9+ LPCs in CCl4-induced liver injury. These findings revealed the role of miR-126 in regulating SOX9+ LPCs fate by targeting Hoxb6 in liver injury repair. Our findings suggest the potential role of miR-126 as a nucleic acid therapy drug target for liver failure.

Keywords: MiR-126; differentiation; injury repair; liver stem cells; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Carbon Tetrachloride
  • Cell Differentiation / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Chronic Disease
  • Dependovirus / metabolism
  • Disease Models, Animal
  • Hepatocytes / cytology
  • Homeodomain Proteins / metabolism*
  • Liver / injuries
  • Liver / metabolism*
  • Liver / physiopathology
  • Liver Regeneration*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / metabolism*
  • NIH 3T3 Cells
  • SOX9 Transcription Factor / metabolism*
  • Stem Cells / metabolism*

Substances

  • Homeodomain Proteins
  • Hoxb6 protein, mouse
  • MIRN126 microRNA, mouse
  • MicroRNAs
  • SOX9 Transcription Factor
  • Carbon Tetrachloride