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

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
• lncRNA
• microRNA
• Treg
• Th17
• RORγt