Human chromosome 21-derived miRNAs are overexpressed in down syndrome brains and hearts

Donald E. Kuhn, Gerard J. Nuovo, Mickey M. Martin, Geraldine E. Malana, Adam P. Pleister, Jinmai Jiang, Thomas D. Schmittgen, Alvin V Terry, Katheleen Gardiner, Elizabeth Head, David S. Feldman, Terry S. Elton

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126 Scopus citations

Abstract

Down syndrome (DS), or Trisomy 21, is the most common genetic cause of cognitive impairment and congenital heart defects in the human population. To date, the contribution of microRNAs (miRNAs) in DS has not been investigated. Bioinformatic analyses demonstrate that human chromosome 21 (Hsa21) harbors five miRNA genes; miR-99a, let-7c, miR-125b-2, miR-155, and miR-802. MiRNA expression profiling, miRNA RT-PCR, and miRNA in situ hybridization experiments demonstrate that these miRNAs are overexpressed in fetal brain and heart specimens from individuals with DS when compared with age- and sex-matched controls. We hypothesize that trisomic 21 gene dosage overexpression of Hsa21-derived miRNAs results in the decreased expression of specific target proteins and contribute, in part, to features of the neuronal and cardiac DS phenotype. Importantly, Hsa21-derived miRNAs may provide novel therapeutic targets in the treatment of individuals with DS.

Original languageEnglish (US)
Pages (from-to)473-477
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume370
Issue number3
DOIs
Publication statusPublished - Jun 6 2008

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Keywords

  • Brain
  • Cardiac
  • Down syndrome
  • In situ hybridization
  • MicroRNA
  • MicroRNA profiling
  • RT-PCR

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Kuhn, D. E., Nuovo, G. J., Martin, M. M., Malana, G. E., Pleister, A. P., Jiang, J., ... Elton, T. S. (2008). Human chromosome 21-derived miRNAs are overexpressed in down syndrome brains and hearts. Biochemical and Biophysical Research Communications, 370(3), 473-477. https://doi.org/10.1016/j.bbrc.2008.03.120