miRNA-PDGFRB/HIF1A-lncRNA CTEPHA1 Network Plays Important Roles in the Mechanism of Chronic Thromboembolic Pulmonary Hypertension

Abstract

Our previous studies have revealed that long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and genes were abnormally expressed in the pulmonary artery tissues of the chronic thromboembolic pulmonary hypertension (CTEPH) patients. We aim to establish the CTEPH-related miRNA-gene-lncRNA network for finding the core genes and associated miRNA and lncRNA in CTEPH patients.Firstly, the target genes of differential miRNAs were predicted by searching TargetScan databases, and the predicted target genes were intersected with the mRNAs from the gene chip. Secondly, the intersective genes were analyzed by the Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway software for obtaining differential intersective genes and then establish the miRNA-gene networks. Thirdly, the possible genes regulated by the differential lncRNAs from the gene chip were intersected with the above-screened mRNA to build the lncRNA-mRNA networks. Subsequently, the miRNA-gene-lncRNA networks were constructed according to the two networks above(miRNA-gene networks and lncRNA-mRNA networks). Finally, the core genes of the networks in the experimental group were screened according to Diffk > 0.6 and used to construct the miRNA-core gene-lncRNA networks of CTEPH.The pathway network, miRNA-mRNA network, lncRNA-mRNA networks, and miRNA-gene-lncRNA networks were successfully constructed. The core genes of the miRNA-gene-lncRNA networks (Diffk > 0.6) were the human Beta-type platelet-derived growth factor receptor (PDGFRB) and hypoxia-inducible factor-1a (HIF-1 A), the miRNAs-PDGFRB-lncRNAs and miRNAs-HIF1A-lncRNAs networks were constructed. Finally, miRNA-149-5p-PDGFRB-TCONS_l2_00020587-XLOC_l2_010723 and miRNA-338-5p/miRNA-199b-5p-HIF1 A-TCONS_l2_00020587-XLOC_l2_010723 were found in the analysis of the network.miRNA-149-5p-PDGFRB-lncRNA CTEPH-associated 1 (CTEPHA1) (TCONS_l2_00020587-XLOC_l2_ 010723) and miRNA-338-5p/miRNA-199b-5p-HIF1A-lncRNA CTEPHA1 are related to the development of CTEPH.(Int Heart J 2019; 60: 924-937)

Circulating MicroRNAs for Diagnosis of Acute Pulmonary Embolism: Still a Long Way to Go

“…Many other biomarkers tested in the last decades failed to replace or improve D-dimer performance [ 55 – 57 ]. Concerning miRNAs, experimental data are mainly focusing on vascular response to APE [ 58 – 63 ], while data on APE predictor/diagnosis are few. The lack of standardization their assay represents an additional confounder.…”

Hypoxia-inducible factor signaling in pulmonary hypertension

“…Among many dysregulated signaling pathways, HIF signaling has been identified as one underlying mechanism determining disease progression not only in pulmonary arterial hypertension (PAH; group I PH), but also in PH due to lung diseases and/or hypoxia, including PH associated with chronic high altitude exposure (5,6), COPD (7), and PF (8) (group III PH). Notably, augmented expression of HIF-1α has been observed in lung tissues of patients with PAH (9-13), chronic thromboembolic PH (14), and idiopathic PF-associated PH (15,16), while HIF-2α has been associated with congenital diaphragmatic hernia-associated PH (17). In addition, neonatal patients with acute respiratory disease-associated PH also display increased circulating levels of HIF-1α (18).…”

Research progress on biomarkers of pulmonary embolism

“…PDGFRB and HIF1A genes are considered to be the most closely related to the development of CTEPH through the miRNA-gene-lncRNA network. 63 Additionly, lncRNA-Ang362 is closely related to pulmonary hypertension. 64…”