Construction and analysis of the abnormal lncRNA–miRNA–mRNA network in hypoxic pulmonary hypertension

Abstract

The incidence of hypoxic pulmonary hypertension (HPH) is increasing. Accumulating evidence suggests that long non-coding RNAs (lncRNAs) play an important role in HPH, but the functions and mechanism have yet to be fully elucidated. In this study, we established an HPH rat model with 8 h of hypoxia exposure (10% O2) per day for 21 days. High-throughput sequencing identified 60 differently expressed (DE) lncRNAs, 20 DE miRNAs and 695 DE mRNAs in rat lung tissue. qRT-PCR verified the accuracy of the results. Immune response, inflammatory response, leukocyte migration, cell cycle, cellular response to interleukin-1, IL-17 signalling pathway, cytokine-cytokine receptor interaction and Toll-like receptor signalling pathway were significantly enriched in DE mRNAs. According to the theory of competing endogenous RNA (ceRNA) networks, lncRNA-miRNA-mRNA network was constructed by Cytoscape software, including 7 lncRNAs, 16 miRNAs and 144 mRNAs. The results suggested that seven DE lncRNAs (Ly6l, AABR07038849.2, AABR07069008.2, AABR07064873.1, AABR07001382.1, AABR07068161.1 and AABR07060341.2) could serve as molecular sponges of the corresponding miRNAs and play a major role in HPH.

Bioinformatic Exploration of Hub Genes and Potential Therapeutic Drugs for Endothelial Dysfunction in Hypoxic Pulmonary Hypertension

“…Additionally, KEGG analysis indicated that PI3K-Akt signaling pathway was significantly enriched, which was consistent with the previous demonstration that hypoxia response involves crosstalk with proliferation and apoptosis mechanisms [20,21]. And research conducted by Liu et al demonstrated that the immune response, inflammatory response, cellular response to interleukins, cell cycle, and leukocyte migration were highly enriched, suggesting that immune and inflammatory response pathways participate in HPH [22], which was partially consistent with the hypoxia-related inflammatory response enriched in this study.…”

Integrative Analyses of Whole-Transcriptome Sequencing Reveals CeRNA Regulatory Network of mRNAs, lncRNAs, miRNAs and circRNAs in Pulmonary Hypertension Treated with FGF21

“…Shuang-Lan Xu et al [28] and Jie Liu et al [29] identi ed the differentially expressed circRNA/miRNA/mRNA and lncRNA/miRNA/mRNA in rat HPH model compared with controls, respectively. Their target genes were enriched in immune and in ammation-related pathways.…”

Endothelial downregulation of nuclear m6A reader YTHDC1 promotes pulmonary vascular remodeling in sugen hypoxia model of pulmonary hypertension

“…Numerous studies increasingly support the idea that lncRNAs play a role in influencing dysfunction in pulmonary arterial endothelial cells (PAECs) and the remodeling of pulmonary vasculature through various pathways [ [44] , [45] , [46] ]. According to the ceRNA hypothesis, the regulatory mechanism involves lncRNAs acting as competitive endogenous RNAs (ceRNAs), influencing gene expression in pulmonary hypertension (PH) through the competition for shared microRNAs (miRNAs) [ 47 , 48 ]. The m6A regulator were involved in the modification of noncoding RNAs [ 49 ].…”