Integrated Bioinformatics and Validation of lncRNA-Mediated ceRNA Network in Myocardial Ischemia/Reperfusion Injury

Myocardial ischemia/reperfusion (MI/R) injury is a common pathology in ischemia heart disease. Long noncoding RNAs (lncRNAs) are significant regulators related to many ischemia/reperfusion conditions. This study is aimed at exploring the molecule mechanism of lncRNA-mediated competing endogenous RNA (ceRNA) network in MI/R.

The dataset profiles of MI/R and normal tissues (GSE130217 and GSE124176) were obtained from the GEO database. Integrated bioinformatics were performed to screen out differentially expressed genes (DEGs). Thereafter, an lncRNA-mediated ceRNA network was constructed by the starBase database. The GO annotations and KEGG pathway analysis were conducted to study action mechanism and related pathways of DEGs in MI/R. A model of hypoxia/reoxygenation- (H/R-) treated HL-1 cell was performed to verify the expression of lncRNAs through qRT-PCR.

2406 differentially expressed- (DE-) mRNAs, 70 DE-lncRNAs, and 156 DE-miRNAs were acquired. These DEGs were conducted to construct an lncRNA-mediated ceRNA network, and a subnetwork including lncRNA Xist/miRNA-133c/mRNA (Slc30a9) was screen out. The functional enrichment analyses revealed that the lncRNAs involved in the ceRNA network might functions in oxidative stress and calcium signaling pathway. The lncRNA Xist expression is reduced under H/R conditions, followed by the increased level of miRNA-133c, thus downregulating the expression of Slc30a9.

In sum, the identified ceRNA network which included the lncRNA Xist/miR-133c/Slc30a9 axis might contribute a better understanding to the pathogenesis and development of MI/R injury and offer a novel targeted therapy way.