title: A deep sequencing approach to uncover the miRNOME in the human heart.
abstract: MicroRNAs (miRNAs) are a class of non-coding RNAs of ∼22 nucleotides in length, and constitute a novel class of gene regulators by imperfect base-pairing to the 3'UTR of protein encoding messenger RNAs. Growing evidence indicates that miRNAs are implicated in several pathological processes in myocardial disease. The past years, we have witnessed several profiling attempts using high-density oligonucleotide array-based approaches to identify the complete miRNA content (miRNOME) in the healthy and diseased mammalian heart. These efforts have demonstrated that the failing heart displays differential expression of several dozens of miRNAs. While the total number of experimentally validated human miRNAs is roughly two thousand, the number of expressed miRNAs in the human myocardium remains elusive. Our objective was to perform an unbiased assay to identify the miRNOME of the human heart, both under physiological and pathophysiological conditions. We used deep sequencing and bioinformatics to annotate and quantify microRNA expression in healthy and diseased human heart (heart failure secondary to hypertrophic or dilated cardiomyopathy). Our results indicate that the human heart expresses >800 miRNAs, the majority of which not being annotated nor described so far and some of which being unique to primate species. Furthermore, >250 miRNAs show differential and etiology-dependent expression in human dilated cardiomyopathy (DCM) or hypertrophic cardiomyopathy (HCM). The human cardiac miRNOME still possesses a large number of miRNAs that remain virtually unexplored. The current study provides a starting point for a more comprehensive understanding of the role of miRNAs in regulating human heart disease.
authors: Department of Cardiology, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.
authors: Stefanos
authors: S
authors: Leptidis
authors: Hamid
authors: H
authors: El Azzouzi
authors: Sjoukje I
authors: SI
authors: Lok
authors: Roel
authors: R
authors: de Weger
authors: Servé
authors: S
authors: Olieslagers
authors: Serv
authors: S
authors: Olieslagers
authors: Natasja
authors: N
authors: Kisters
authors: Gustavo J
authors: GJ
authors: Silva
authors: Stephane
authors: S
authors: Heymans
authors: Edwin
authors: E
authors: Cuppen
authors: Eugene
authors: E
authors: Berezikov
authors: Leon J
authors: LJ
authors: De Windt
authors: Paula
authors: P
authors: da Costa Martins
mesh_terms: D002311:Cardiomyopathy, Dilated / Q000235:genetics; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology
chemical_list: D035683:MicroRNAs