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Biochem Biophys Res Commun. 2008 Jun 6;370(3):473-7. doi: 10.1016/j.bbrc.2008.03.120. Epub 2008 Apr 1.

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

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  • 1Davis Heart and Lung Research Institute, The Ohio State University, DHLRI 515, 473 West 12th Avenue, Columbus, OH 43210, USA.

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.

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PMID:
18387358
[PubMed - indexed for MEDLINE]
PMCID:
PMC2585520
Free PMC Article
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