Construction and analysis of the lncRNA‑miRNA‑mRNA network based on competitive endogenous RNA reveals functional genes in heart failure - PubMed (original) (raw)

Construction and analysis of the lncRNA‑miRNA‑mRNA network based on competitive endogenous RNA reveals functional genes in heart failure

Guohong Wang et al. Mol Med Rep. 2019 Feb.

Abstract

Heart failure (HF) is a principal cause of morbidity and mortality worldwide, affecting an estimated 38 million people. Although significant progress has been made with respect to the underlying molecular mechanisms, the role of the competing endogenous RNA (ceRNA) network in the pathogenesis of HF remains largely unknown. In this study, an HF‑associated ceRNA network was constructed based on the differentially expressed long noncoding RNAs (lncRNAs), microRNAs (miRNAs) and mRNAs obtained, respectively, from the GSE77399, GSE104150 and GSE84796 datasets. The ceRNA network consisted of 12 lncRNA nodes, 43 miRNA nodes, 343 mRNA nodes and 530 edges. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that the ceRNA network was primarily enriched in the immune response, inflammatory response and T cell and B cell receptor signaling pathways. In addition, three lncRNAs (growth arrest specific 5, taurine upregulated 1 and HOX transcript antisense RNA) and three miRNAs [hsa‑miRNA (miR)‑26b‑5p, hsa‑miR‑8485 and hsa‑miR‑940] with higher node degrees compared with other genes were selected as hub nodes. The expression of hub nodes in patients with HF was verified by reverse transcription‑quantitative polymerase chain reaction analysis. The present study provided further insights into the important roles of the ceRNA network in HF development, and indicated the potential use of these hub nodes as diagnostic biomarkers and therapeutic targets.

Keywords: heart failure; miRNA; long noncoding RNA; competing endogenous RNA.

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Figures

Figure 1.

Figure 1.

lncRNA-miRNA-mRNA competing endogenous RNA network of upregulated miRNAs. The squares represent lncRNAs, the circles represent miRNAs and the rhombuses represent mRNAs. There were six lncRNA nodes, 17 miRNA nodes and 107 mRNA nodes in the network. miRNA, microRNA; lncRNA, long noncoding RNA.

Figure 2.

Figure 2.

Top three miRNAs ranked by node degree. The sub-networks of (A) hsa-miR-26b-5p, (B) hsa-miR-8485 and (C) hsa-let-7a-5p are presented. The circles represent miRNAs, the squares represent long noncoding RNAs and the rhombuses represent mRNAs. miR/miRNA, microRNA.

Figure 3.

Figure 3.

GO enrichment analysis. (A) Downregulated miRNA ceRNA network. (B) Upregulated miRNA ceRNA network. GO analysis classified the differentially expressed genes into three groups, including biological process, cellular component and molecular function. GO, gene ontology; miRNA, microRNA; ceRNA, competing endogenous RNA.

Figure 4.

Figure 4.

Kyoto Encyclopedia of Genes and Genomes pathway analysis. The triangles represent the downregulated miRNA ceRNA network and the circles represent the upregulated miRNA ceRNA network. miRNA, microRNA; ceRNA, competing endogenous RNA.

Figure 5.

Figure 5.

Hub nodes detection by reverse transcription-quantitative polymerase chain reaction. (A) The relative expression of hsa-miR-26b-5p and hsa-miR-8485 was decreased, and hsa-miR-940 was increased, in patients with HF. (B) The relative expression of GAS5 and Hotair was, increased and TUG1 was decreased, in patients with HF. The data indicate the mean ± standard deviation of triplicate samples, from three independent experiments. **P<0.01, ***P<0.001 vs. respective control group. HF, heart failure; miRNA/miR, microRNA; lncRNA, long noncoding RNA; GAS5, growth arrest specific 5; TUG1, taurine upregulated 1; Hotair, HOX transcript antisense RNA.

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