Downregulation of microRNA-592 protects mice from hypoplastic heart and congenital heart disease by inhibition of the Notch signaling pathway through upregulating KCTD10

J Cell Physiol. 2019 May;234(5):6033-6041. doi: 10.1002/jcp.27190. Epub 2018 Nov 27.

Abstract

Evidence has demonstrated that the microRNA (miR) may play a significant role in the development of congenital heart disease (CHD). Here, we explore the mechanism of microRNA-592 (miR-592) in heart development and CHD with the involvement of KCTD10 and Notch signaling pathway in a CHD mouse model. Cardiac tissues were extracted from CHD and normal mice. Immunohistochemistry staining was performed to detect positive expression rate of KCTD10. A series of inhibitor, activators, and siRNAs was introduced to verified regulatory functions for miR-592 governing KCTD10 in CHD. Furthermore, the effect of miR-592 on cell proliferation and apoptosis was also investigated. Downregulated positive rate of KCTD10 was observed in CHD mice. Downregulation of miR-592 would upregulate expression of KCTD10 and inhibit the activation of Notch signaling pathway, thus promote cell proliferation. This study demonstrates that downregulation of miR-592 prevents CHD and hypoplastic heart by inhibition of the Notch signaling pathway via negatively binding to KCTD10.

Keywords: KCTD10; MmicroRNA-592; apoptosis; congenital heart disease; endocardium cells; heart development; notch signaling pathway; proliferation.

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Apoptosis
  • Basic Helix-Loop-Helix Proteins / genetics
  • Basic Helix-Loop-Helix Proteins / metabolism
  • Binding Sites
  • Cell Proliferation
  • Cells, Cultured
  • Disease Models, Animal
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Developmental
  • Heart Defects, Congenital / genetics
  • Heart Defects, Congenital / metabolism
  • Heart Defects, Congenital / pathology
  • Heart Defects, Congenital / prevention & control*
  • Jagged-1 Protein / genetics
  • Jagged-1 Protein / metabolism
  • Male
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Potassium Channels, Voltage-Gated / genetics
  • Potassium Channels, Voltage-Gated / metabolism*
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Signal Transduction
  • Transcription Factor HES-1 / genetics
  • Transcription Factor HES-1 / metabolism

Substances

  • 3' Untranslated Regions
  • Basic Helix-Loop-Helix Proteins
  • Jagged-1 Protein
  • MicroRNAs
  • Potassium Channels, Voltage-Gated
  • Receptors, Notch
  • Repressor Proteins
  • Transcription Factor HES-1
  • Hes1 protein, mouse
  • Hey2 protein, mouse
  • Jag1 protein, mouse
  • KCTD10 protein, mouse
  • MIRN592 microRNA, mouse