Integrative analysis reveals key mRNA and long non-coding RNA interaction in idiopathic pulmonary arterial hypertension

Abstract

IntroductionIdiopathic pulmonary arterial hypertension (IPAH) is a rare and sporadic form of pulmonary arterial hypertension (PAH), characterized by elevated pulmonary arterial resistance leading to right heart failure. However, molecular mechanisms of PAH development are still not completely understood.Material and methodsIn this study, we aimed to uncover key mRNAs and long non-coding RNA (lncRNAs), functional modules and pathways. Moreover, to detect the dysregulated pathway or biological function, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. PPI and co-expression networks were constructed to reveal the potential roles of PAH-related mRNAs and lncRNAs.ResultsA total of 3,134 genes, including 945 up-regulated and 2,189 down-regulated genes, were identified to be differentially expressed in IPAH by differential expression analysis. We identified T cell differentiation and the T cell receptor signaling pathway as up-regulated in IPAH by using GO and KEGG analysis. Based on the PPI module analysis, we identified that the pro-inflammatory genes, such as OAS1, CXCL10, STAT1 and TLR4, were the hub genes in the PPI modules. To link the lncRNAs to the PPI modules, we calculated the Spearman correlation coefficient for lncRNA-DE-mRNA pairs to identify the modules with high correlation with each lncRNA.ConclusionsNotably, 6 of these lncRNAs were associated with modules characterized by the NOD-like receptor signaling pathway and chemokine signaling pathway, suggesting that these lncRNAs may promote the occurrence of IPAH via participating in the pro-inflammatory pathways. In conclusion, our systematic analysis not only improved our understanding of the molecular mechanism, but also provided potential lncRNA biomarkers for further research.

Roles of LncRNAs in the Pathogenesis of Pulmonary Hypertension

“…One need to supplement is idiopathic PAH (IPAH), IPAH patients are essentially PAH patients, and research has revealed a close relationship between lncRNAs and iPAH. Major dysregulated pathways were found, and important lncRNAs involved in PAH were highlighted by Wang et al .’s [ 134 ] systematic data analysis of lncRNAs in IPAH peripheral blood monocytes (PBMCs). Using differential expression and further studies, the researchers found 18 pairs of lncRNAs and PPI modules.…”