Construction of asthma related competing endogenous RNA network revealed novel long non-coding RNAs and potential new drugs

Respir Res. 2020 Jan 10;21(1):14. doi: 10.1186/s12931-019-1257-x.

Abstract

Background: Asthma is a heterogeneous disease characterized by chronic airway inflammation. Long non-coding RNA can act as competing endogenous RNA to mRNA, and play significant role in many diseases. However, there is little known about the profiles of long non-coding RNA and the long non-coding RNA related competing endogenous RNA network in asthma. In current study, we aimed to explore the long non-coding RNA-microRNA-mRNA competing endogenous RNA network in asthma and their potential implications for therapy and prognosis.

Methods: Asthma-related gene expression profiles were downloaded from the Gene Expression Omnibus database, re-annotated with these genes and identified for asthma-associated differentially expressed mRNAs and long non-coding RNAs. The long non-coding RNA-miRNA interaction data and mRNA-miRNA interaction data were downloaded using the starBase database to construct a long non-coding RNA-miRNA-mRNA global competing endogenous RNA network and extract asthma-related differentially expressed competing endogenous RNA network. Finally, functional enrichment analysis and drug repositioning of asthma-associated differentially expressed competing endogenous RNA networks were performed to further identify key long non-coding RNAs and potential therapeutics associated with asthma.

Results: This study constructed an asthma-associated competing endogenous RNA network, determined 5 key long non-coding RNAs (MALAT1, MIR17HG, CASC2, MAGI2-AS3, DAPK1-IT1) and identified 8 potential new drugs (Tamoxifen, Ruxolitinib, Tretinoin, Quercetin, Dasatinib, Levocarnitine, Niflumic Acid, Glyburide).

Conclusions: The results suggested that long non-coding RNA played an important role in asthma, and these novel long non-coding RNAs could be potential therapeutic target and prognostic biomarkers. At the same time, potential new drugs for asthma treatment have been discovered through drug repositioning techniques, providing a new direction for the treatment of asthma.

Keywords: Asthma; Competing endogenous RNA network; Drug repositioning; Long non-coding RNA; mRNA.

MeSH terms

  • Anti-Asthmatic Agents / chemical synthesis
  • Anti-Asthmatic Agents / metabolism
  • Anti-Asthmatic Agents / therapeutic use*
  • Asthma / drug therapy*
  • Asthma / genetics*
  • Asthma / metabolism
  • Gene Regulatory Networks / drug effects
  • Gene Regulatory Networks / physiology*
  • Humans
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Transcriptome / drug effects
  • Transcriptome / physiology*

Substances

  • Anti-Asthmatic Agents
  • RNA, Long Noncoding