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

Mol Med Rep. 2019 Feb;19(2):994-1003. doi: 10.3892/mmr.2018.9734. Epub 2018 Dec 10.

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.

MeSH terms

  • Aged
  • Case-Control Studies
  • Databases, Genetic
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Ontology
  • Gene Regulatory Networks*
  • Heart Failure / genetics*
  • Heart Failure / immunology
  • Heart Failure / pathology
  • Humans
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / immunology
  • Molecular Sequence Annotation
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / immunology
  • RNA, Messenger / genetics*
  • RNA, Messenger / immunology
  • Receptors, Antigen, B-Cell / genetics
  • Receptors, Antigen, B-Cell / immunology
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • Signal Transduction

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Messenger
  • Receptors, Antigen, B-Cell
  • Receptors, Antigen, T-Cell