Expression profiling and ontology analysis of long noncoding RNAs in post-ischemic heart and their implied roles in ischemia/reperfusion injury.

Abstract

Long noncoding RNAs (lncRNAs) play important regulatory roles in cellular physiology. The contributions of lncRNAs to ischemic heart disease remain largely unknown. The aim of this study was to investigate the profile of myocardial lncRNAs and their potential roles at early stage of reperfusion. lncRNAs and mRNAs were profiled by microarray and the expression of some highly-dysregulated lncRNAs was further validated using polymerase chain reaction. Our results revealed that 64 lncRNAs were up-regulated and 87 down-regulated, while 50 mRNAs were up-regulated and 60 down-regulated in infarct region at all reperfusion sampled. Gene ontology analysis indicated that dysregulated transcripts were associated with immune response, spermine catabolic process, taxis, chemotaxis, polyamine catabolic process, spermine metabolic process, chemokine activity and chemokine receptor binding. Target gene-related pathway analysis showed significant changes in cytokine-cytokine receptor interaction, the chemokine signaling pathway and nucleotide oligomerization domain (NOD)-like receptor signaling pathway which have a close relationship with myocardial ischemia/reperfusion injury (MI/RI). Besides, a gene co-expression network was constructed to identify correlated targets of 10 highly-dysregulated lncRNAs. These lncRNAs may play their roles by this network in post-ischemic heart. Such results provide a foundation for understanding the roles and mechanisms of myocardial lncRNAs at early stage of reperfusion.