The long non-coding RNA landscape of cardiac regeneration in zebrafish.
- Cardiovascular Research Unit
BACKGROUND: Novel therapeutic targets of heart failure (HF) are needed. Long non-coding RNAs (lncRNAs) are engaged during cardiac regeneration. Unlike in humans, zebrafish naturally undergo cardiac regeneration following HF. We aimed to describe the landscape of lncRNAs during regeneration in a zebrafish model of HF and to investigate their human homolog. METHODS: HF was established in adult zebrafish through tri-weekly incubations with an anemia inducing drug - phenylhydrazine hydrochloride (PHZ). After 5 weeks, PHZ treatment ceased and fish were followed through a regeneration period of 14 days. Total RNA was extracted from the hearts of adult zebrafish after establishment of HF and at 2, 5 and 9 days after treatment cessation (9 hearts per condition at each timepoint). Gene regulation patterns were characterized using bioinformatics and validated by quantitative PCR. RESULTS: We obtained 14,340 lncRNAs from re-annotated Affymetrix zebrafish microarray. Of these, 187 lncRNAs were found differentially expressed (false discovery rate < 0.05 and fold change >/= 2) at at least one time point. 85% of differentially expressed lncRNAs overlapped or were close to (distance < 10kb) protein-coding genes which were mostly related to muscle development in Gene Ontology analyses. 57 lncRNAs had human homologs according to orientation relative to their conserved protein coding neighbours. CONCLUSIONS: LncRNAs are differentially expressed during regeneration following HF in adult zebrafish and could be potential future therapeutic targets. The extent to which lncRNAs contribute to cardiac regeneration is a worthy avenue for future research.