the role of micrornas, a group of small non-coding rnas, in downs syndrome

downs 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 over-expressed 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 over-expression of hsa21-derived mirnas results in the decreased expression of specific target proteins and contributes, in part, to neuronal and cardiac phenotypic features of ds. more importantly, hsa21-derived mirnas may provide novel therapeutic targets in the treatment of individuals with ds.