LncRNA-MEG3 functions as a competing endogenous RNA to regulate Treg/Th17 balance in patients with asthma by targeting microRNA-17/ RORγt

Biomed Pharmacother. 2019 Mar;111:386-394. doi: 10.1016/j.biopha.2018.12.080. Epub 2018 Dec 26.

Abstract

Background: Treg/Th17 imbalance plays an essential role in the pathogenesis of asthma. Disordered LncRNAs were observed in asthma, however, whether LncRNAs can regulate the Treg/Th17 balance and its mechanism still needs to be investigated.

Methods: Microarrays were performed to identify the differentially expressed lncRNAs and microRNAs in peripheral blood CD4 + T cells from patients with asthma and healthy controls. Bioinformatical evidence was used to select candidate lncRNAs and microRNAs which may involve in regulation of Treg/Th17 balance. The function of LncRNA-MEG3 and microRNA-17 on the alteration of the CD4 + T cell population were determined in vitro experiments. Meanwhile, the regulatory effect of LncRNA-MEG3 and microRNA-17 on RORγt or Foxp3 was estimated. The interaction of LncRNA-MEG3 with microRNA-17 was confirmed by dual luciferase reporter assay and RNA pull-down.

Results: 25 lncRNAs and 19 microRNAs were selected as candidate genes which differentially expressed in CD4 + T cells from patients with asthma compared with healthy controls and had potential to control Treg/Th17 balance by regulating RORγt or Foxp3. Alternation of LncRNA-MEG3 changed the function and increased the percentage of Th17. LncRNA-MEG3 could regulate the RORγt mRNA and protein level. LncRNA-MEG3 could inhibit the level of microRNA-17 as a competing endogenous RNA (ceRNA). microRNA-17 suppressed Th17 though targeting RORγt directly.

Conclusion: LncRNA-MEG3 can sponge microRNA-17 as a ceRNA, thereby regulating RORγt and ultimately affecting Treg/Th17 balance in asthma. The lncRNA/microRNA axis may have potential application in clinical treatment and diagnosis of the disease.

Keywords: Asthma; Foxp3; RORγt; Th17; Treg; lncRNA; microRNA.

MeSH terms

  • Adult
  • Asthma / genetics
  • Asthma / metabolism*
  • Female
  • Humans
  • Male
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Middle Aged
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / biosynthesis*
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
  • RNA / biosynthesis
  • RNA / genetics
  • RNA, Long Noncoding / biosynthesis*
  • RNA, Long Noncoding / genetics
  • T-Lymphocytes, Regulatory / physiology*
  • Th17 Cells / physiology*

Substances

  • MEG3 non-coding RNA, human
  • MIRN17 microRNA, human
  • MicroRNAs
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • RNA, Long Noncoding
  • RORC protein, human
  • RNA