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Human chromosome 21-derived miRNAs are overexpressed in down syndrome brains and hearts |
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| Authors: | Kuhn Donald E Nuovo Gerard J Martin Mickey M Malana Geraldine E Pleister Adam P Jiang Jinmai Schmittgen Thomas D Terry Alvin V Gardiner Katheleen Head Elizabeth Feldman David S Elton Terry S |
| Affiliation: | a Davis Heart and Lung Research Institute, The Ohio State University, DHLRI 515, 473 West 12th Avenue, Columbus, OH 43210, USA b College of Pharmacy, Division of Pharmacology, The Ohio State University, DHLRI 515, 473 West 12th Avenue, Columbus, OH 43210, USA c College of Medicine, Department of Pathology, The Ohio State University, DHLRI 515, 473 West 12th Avenue, Columbus, OH 43210, USA d College of Pharmacy, Division of Pharmaceutics, The Ohio State University, DHLRI 515, 473 West 12th Avenue, Columbus, OH 43210, USA e Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, GA 30912, USA f Department of Medicine, Division of Cardiology, The Ohio State University, DHLRI 515, 473 West 12th Avenue, Columbus, OH 43210, USA g Department of Medicine, Division of Cardiovascular Medicine, The Ohio State University, DHLRI 515, 473 West 12th Avenue, Columbus, OH 43210, USA h Department of Pediatrics, University of Colorado at Denver and the Health Sciences Center, Aurora, CO 80045, USA i Institute for Brain Aging and Dementia, Department of Neurology, University of California, Irvine, 1259 Gillespie Neuroscience Facility, Irvine, CA 92697, 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. |
| Keywords: | Down syndrome MicroRNA MicroRNA profiling RT-PCR In situ hybridization Cardiac Brain |
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