Revealing the ceRNA Regulatory Network in A Rat Model of Hypoxic Pulmonary Hypertension
DOI:
https://doi.org/10.52547/aha26074Keywords:
Hypoxic pulmonary hypertension, pulmonary artery smooth muscle cells, lncRNA, miRNA, ceRNA network, hypoxiaAbstract
Abstract
Background:
Hypoxic pulmonary hypertension (HPH) is a disease characterized by excessive proliferation of lung blood vessel cells, including lung smooth muscle cells, which can lead to death in severe hypoxia. The purpose of this study was to construct the lncRNA-miRNA-mRNA regulatory network of key genes by using the sequencing data of rat smooth muscle cells under hypoxia and normal conditions, and to clarify its mechanism of action.
Methods:
In this study, differences of long non-coding RNA (lncRNA), micro RNA (miRNA) and mRNA in HPH samples and control samples were analyzed. Then the lncRNA-miRNA-mRNA relationship network was constructed based on sequence matching and regulatory relationship. Afterthat, key genes were screened by protein-protein interaction (PPI) analysis, and gene set enrichment analysis (GSEA), correlation analysis, and drug prediction were performed for key genes. Finally, lncRNA-miRNA-mRNA subnetworks containing key genes were established.
Results:
In this study, five key genes were extracted from 76 mRNAs in the PPI network, namely Pdgfra, Dpp4, Irf1, Edn1 and Csf1. According to correlation analysis, Pdgfra, Dpp4, Irf1 and Csf1 were positively correlated with the other 4 genes, while Edn1 was negatively correlated with the other 4 genes. GSEA enrichment analysis showed that five key genes might be involved in galactose metabolism and steroid biosynthesis. In addition, the drug prediction results of key genes showed that the gene Pdgfra was stable in combination with multiple pairs of drugs such as AVAPRITINIB, which was expected to become a targeted drug. Finally, a competing endogenous RNA (ceRNA) subnetwork was constructed, and the results showed that lncRNA (NONRATT000872.2 and NONRATT030918.2) competitively bound miRNA (MoMir-301b-3P) with mRNA (Pdgfra, Dpp4, Irf1, and Csf1).
Conclusion:
In this study, whole transcriptome data and small RNA data of rat smooth muscle cells under hypoxia/normal conditions were used to construct lncRNA-miRNA-mRNA regulatory network containing key genes, providing theoretical basis for the treatment of PHA.
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References
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Data Availability Statement
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