Genome-wide profiling of the cardiac transcriptome after myocardial infarction identifies novel heart-specific long non-coding RNAs.

Détails

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Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_325D626A9663
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Genome-wide profiling of the cardiac transcriptome after myocardial infarction identifies novel heart-specific long non-coding RNAs.
Périodique
European Heart Journal
Auteur(s)
Ounzain S., Micheletti R., Beckmann T., Schroen B., Alexanian M., Pezzuto I., Crippa S., Nemir M., Sarre A., Johnson R., Dauvillier J., Burdet F., Ibberson M., Guigó R., Xenarios I., Heymans S., Pedrazzini T.
ISSN
1522-9645 (Electronic)
ISSN-L
0195-668X
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
36
Numéro
6
Pages
353-68a
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
AIM: Heart disease is recognized as a consequence of dysregulation of cardiac gene regulatory networks. Previously, unappreciated components of such networks are the long non-coding RNAs (lncRNAs). Their roles in the heart remain to be elucidated. Thus, this study aimed to systematically characterize the cardiac long non-coding transcriptome post-myocardial infarction and to elucidate their potential roles in cardiac homoeostasis.
METHODS AND RESULTS: We annotated the mouse transcriptome after myocardial infarction via RNA sequencing and ab initio transcript reconstruction, and integrated genome-wide approaches to associate specific lncRNAs with developmental processes and physiological parameters. Expression of specific lncRNAs strongly correlated with defined parameters of cardiac dimensions and function. Using chromatin maps to infer lncRNA function, we identified many with potential roles in cardiogenesis and pathological remodelling. The vast majority was associated with active cardiac-specific enhancers. Importantly, oligonucleotide-mediated knockdown implicated novel lncRNAs in controlling expression of key regulatory proteins involved in cardiogenesis. Finally, we identified hundreds of human orthologues and demonstrate that particular candidates were differentially modulated in human heart disease.
CONCLUSION: These findings reveal hundreds of novel heart-specific lncRNAs with unique regulatory and functional characteristics relevant to maladaptive remodelling, cardiac function and possibly cardiac regeneration. This new class of molecules represents potential therapeutic targets for cardiac disease. Furthermore, their exquisite correlation with cardiac physiology renders them attractive candidate biomarkers to be used in the clinic.
Mots-clé
Analysis of Variance, Animals, Biomarkers/metabolism, Cell Differentiation/physiology, Cells, Cultured, Chromatin/genetics, Embryonic Stem Cells/cytology, Gene Expression Profiling/methods, Humans, Male, Mice, Inbred C57BL, Myocardial Infarction/genetics, RNA, Long Noncoding/genetics, RNA, Long Noncoding/metabolism, Transcriptome/genetics, Transfection, Vascular Remodeling/genetics
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/04/2015 17:24
Dernière modification de la notice
20/08/2019 13:17
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