MiRNA-145 Regulates the Development of Congenital Heart Disease Through Targeting FXN

Pediatr Cardiol. 2016 Apr;37(4):629-36. doi: 10.1007/s00246-015-1325-z. Epub 2015 Dec 30.

Abstract

Congenital heart disease (CHD) is the leading cause of death in infants in the world. The study of CHDs has come a long way since their classification and description. Although transcriptional programmes that are impaired in individuals with CHDs are being identified, the mechanisms of how these deficiencies translate to a structural defect are unknown. In this study, using high-throughput microarray analysis and molecular network analysis, FXN was identified to be the most differentially expressed key gene in CHD. By TargetScan analysis, we predicted FXN was the target gene of miRNA-145 and miRNA-182. Through real-time PCR analysis of clinical samples and experiments in cell lines, we confirmed that miRNA-145 but not miRNA-182 directly binds to the 3' UTR region of FXN and negatively regulates its expression. We further found that through targeting FXN, miRNA-145 regulates apoptosis and mitochondrial function. In general, our study confirmed the differentially expressed FXN regulates the development of CHD and the differential expression was under the control of miRNA-145. These results might provide new insight into the understanding of the CHD pathogenesis and may facilitate further therapeutic studies.

Keywords: Congenital heart disease; FXN; MiRNA-145.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics*
  • Case-Control Studies
  • Child
  • Child, Preschool
  • China
  • Female
  • Gene Regulatory Networks
  • Heart Defects, Congenital / genetics*
  • Humans
  • Iron-Binding Proteins / genetics*
  • Male
  • MicroRNAs / genetics*
  • Microarray Analysis

Substances

  • 3' Untranslated Regions
  • Iron-Binding Proteins
  • MIRN145 microRNA, human
  • MicroRNAs
  • frataxin