Aim: The present study aimed to investigate whether long non-coding RNAs (lncRNAs) are involved in cardiac fibrogenesis induced by myocardial infarction (MI). Methods: The differentially expressed lncRNAs and mRNAs in peri-infarct region of mice 4 weeks after myocardial infarction (MI) were selected for bioinformatic analysis including gene ontology (GO) enrichment, pathway and network analysis. Results:Left ventricular tissue levels of lncRNAs and mRNAs were compared between MI and sham control mice, using a false discovery rate of < 5%. Out of 55,000 lncRNAs detected, 263 were significantly up-regulated and 282 down-regulated. Out of 23,000 mRNAs detected, 142 were significantly up-regulated and 67 down-regulated. Among the differentially expressed lncRNAs, 53 were up-regulated by ≥ 2.0-fold change and 37 down-regulated by ≤0.5-fold change. Nine up-regulated and 5 down-regulated lncRNAs were randomly selected for qRT-PCR verification. GO and pathway analyses revealed 173 correlated lncRNA-mRNA pairs for 57 differentially expressed lncRNAs and 20 differentially expressed genes which are related to the development of cardiac fibrosis. We identified TGF-β3 as the top-ranked gene, a critical component of the TGF-β and MAPK signaling pathways in cardiac fibrosis. NONMMUT022554 was identified as the top-ranked lncRNA, positively correlated with 6 up-regulated genes, which are involved in the extracellular matrix-receptor interactions and the PI3K-Akt signaling pathway. Conclusion: Our study has identified the expression signature of lncRNAs in cardiac fibrosis induced by MI and unraveled the possible involvement of the deregulated lncRNAs in cardiac fibrosis and the associated pathological processes.
- Copyright 2016 The Author(s)
Archiving permitted only in line with the archiving policy of Portland Press Limited. The final version of record will be available under the Creative Commons Attribution Licence 3.0. You are encouraged to use the final version of record.