RETRACTED: Human chromosome 21-derived miRNAs are overexpressed in down syndrome brains and hearts (Retracted article. See vol. 436, pg. 564, 2013)

被引:120
作者
Kuhn, Donald E. [2 ]
Nuovo, Gerard J. [2 ,3 ]
Martin, Mickey M. [2 ]
Malana, Geraldine E. [2 ]
Pleister, Adam P. [2 ]
Jiang, Jinmai [4 ]
Schmittgen, Thomas D. [4 ]
Terry, Alvin V., Jr. [6 ]
Gardiner, Katheleen [8 ,9 ]
Head, Elizabeth [10 ]
Feldman, David S. [1 ,2 ]
Elton, Terry S. [2 ,5 ,7 ]
机构
[1] Ohio State Univ, Dept Med, Div Cardiol, Columbus, OH 43210 USA
[2] Ohio State Univ, Davis Heart & Lung Res Inst, Columbus, OH 43210 USA
[3] Ohio State Univ, Coll Med, Dept Pathol, Columbus, OH 43210 USA
[4] Ohio State Univ, Coll Pharm, Div Pharmaceut, Columbus, OH 43210 USA
[5] Ohio State Univ, Coll Pharm, Div Pharmacol, Columbus, OH 43210 USA
[6] Med Coll Georgia, Dept Pharmacol & Toxicol, Augusta, GA 30912 USA
[7] Ohio State Univ, Dept Med, Div Cardiovasc Med, Columbus, OH 43210 USA
[8] Univ Colorado Denver, Dept Pediat, Aurora, CO 80045 USA
[9] Hlth Sci Ctr, Aurora, CO 80045 USA
[10] Univ Calif Irvine, Inst Brain Aging & Dementia, Dept Neurol, Gillespie Neurosci Facil 1259, Irvine, CA 92697 USA
关键词
down syndrome; microRNA; microRNA profiling; RT-PCR; in situ hybridization; cardiac; brain;
D O I
10.1016/j.bbrc.2008.03.120
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (c) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:473 / 477
页数:5
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