Network construction of aberrantly expressed miRNAs and their target mRNAs in ventricular myocardium with ischemia–reperfusion arrhythmias

Abstract

Background: Increasing evidences have verified that microRNAs (miRNAs) play an important role in formation and progression of various cardiac diseases including arrhythmias. Existing research has showed that certain miRNAs exhibit significantly different expressions and effects in arrhythmias. However, the effect of miRNAs in the progression of hypothermic ischemic–reperfusion arrhythmias (RA) and its potential mechanism remains to be further discussed. Methods: By utilizing a model for hypothermic ischemia–reperfusion of rats, miRNAs expression profiles of ventricular myocardium with global hypothermic ischemia–reperfusion and those of ventricular myocardium with hypothermic ischemia–RA were established through high-throughput sequencing. Furthermore, the aberrantly expressed miRNAs in myocardium with and without hypothermic ischemia–RA were screened and verified. By applying RNAhybrid, MiRanda, and TargetScan software, the target genes of these aberrantly expressed miRNAs were predicted. Based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, the mRNA targets associated with these miRNAs were determined and the miRNA–mRNA interaction during the progression of cardiovascular diseases was explored. The aberrantly expressed miRNAs related to hypothermic ischemia–RA were validated by employing quantitative fluorescence polymerase chain reaction (PCR). Results: Eight significantly aberrantly expressed miRNAs were identified(novel-miR-1 、novel-miR-16、novel-miR-17、novel-miR-19、novel-miR-30、novel-miR-43、rno-miR-122-5p、rno-miR-429), in which six were up-regulated and two were down-regulated. Moreover, target genes and signaling pathways associated with these aberrantly expressed miRNAs were predicted and analyzed. According to miRNA–mRNA interaction network graph, it was revealed that GJA1 gene was considered as the target of novel-miR-17. Conclusions: Aberrantly expressed miRNAs were possibly associated with the formation mechanism of hypothermic ischemia–RA. Specific miRNAs, such as novel-miR-17 and rno-miR-429 are probably new potential targets for further conducting functional study on hypothermic ischemia–RA.