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A Deep Sequencing Approach to Uncover the miRNOME in the Human Heart

Leptidis, S., el Azzouzi, H., Lok, S. I., de Weger, R., Olieslagers, S., Kisters, N., Silva, G. J., Heymans, S., Cuppen, E., Berezikov, E., De Windt, L. J. & Martins, P. D. C., 27-Feb-2013, In : PLoS ONE. 8, 2, 9 p., e57800.

Research output: Contribution to journalArticleAcademicpeer-review

  • Stefanos Leptidis
  • Hamid el Azzouzi
  • Sjoukje I. Lok
  • Roel de Weger
  • Serv Olieslagers
  • Natasja Kisters
  • Gustavo J. Silva
  • Stephane Heymans
  • Edwin Cuppen
  • Eugene Berezikov
  • Leon J. De Windt
  • Paula da Costa Martins

MicroRNAs (miRNAs) are a class of non-coding RNAs of similar to 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.

Original languageEnglish
Article numbere57800
Number of pages9
JournalPLoS ONE
Volume8
Issue number2
Publication statusPublished - 27-Feb-2013
Externally publishedYes

    Keywords

  • EMBRYONIC STEM-CELLS, CARDIAC-HYPERTROPHY, SMALL RNAS, CARDIOVASCULAR-DISEASE, MYOCARDIAL-INFARCTION, MICRORNA EXPRESSION, IDENTIFICATION, DISCOVERY, MIR-145, GENES

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