LncRNATUG1 Facilitates Th2 Cell Differentiation by Targeting the miR-29c/B7-H3 Axis on Macrophages

Abstract

The role of long non-coding RNAs (lncRNA) in asthma remains unclear. In this study, we examined the role of long non-coding RNA taurine upregulated 1 (lncRNA TUG1) in asthma. We found that lncRNA TUG1 is one of the differentially expressed lncRNAs in the monocytes of asthmatic children and is associated with Th cell differentiation. LncRNA TUG1 and miR-29c are mainly distributed in the cytoplasm of macrophages. Our data suggested that lncRNA TUG1 increased in macrophages stimulated by House Dust Mite in a dose-dependent manner. Using loss- and gain of function strategy, we found that miR-29c might regulate Th2 cell differentiation by directly targeting co-stimulatory molecule B7-H3. Furthermore, down-regulation of lncRNA TUG1 decreased the level of GATA3 in CD4+T cells and was associated with miR-29c/B7-H3 axis. Moreover, the dual-luciferase reporter assay confirmed that lncRNA TUG1 serves as a competing endogenous RNA to sponge miR-29c. According to the rescue experiment, lncRNA TUG1 regulated Th2 cell differentiation via miR-29c. These data suggest that lncRNA TUG1 in macrophages regulates Th2 cell differentiation via miR-29c/B7-H3 axis.

Unlocking the secrets of long non-coding RNAs in asthma

“…By performing in vitro experiments on macrophages, they demonstrated that TUG1 sponges microRNA-29c, which has been linked to Th2 cell differentiation. 56 By using a rat model, Lin et al studied the function of TUG1 in asthma. 57 TUG1 was upregulated in the ASMCs of an asthma M2 macrophage activation 75 ASMC, airway smooth muscle cell; lncRNA, long non-coding RNA; PBMC, peripheral blood mononuclear cell.…”

“…Sun et al observed that TUG1 is differentially expressed in monocytes of children with asthma. By performing in vitro experiments on macrophages, they demonstrated that TUG1 sponges microRNA-29c, which has been linked to Th2 cell differentiation 56…”

The Novel Regulatory Role of the lncRNA–miRNA–mRNA Axis in Chronic Inflammatory Airway Diseases

“…LncRNAs and miRNAs alone have been shown to play regulatory roles in asthma by regulating CD4 + T-cell function ( Wang et al, 2021c ). Notably, three studies observed a novel regulatory role of lncRNAs targeting miRNAs in regulating the Th1/Th2 balance ( Liang and Tang, 2020 ; Wei et al, 2020 ; Sun et al, 2021 ). For example, Sun et al ( Sun et al, 2021 ) observed that TUG1 is differentially expressed in the monocytes of asthmatic children.…”

“…Notably, three studies observed a novel regulatory role of lncRNAs targeting miRNAs in regulating the Th1/Th2 balance ( Liang and Tang, 2020 ; Wei et al, 2020 ; Sun et al, 2021 ). For example, Sun et al ( Sun et al, 2021 ) observed that TUG1 is differentially expressed in the monocytes of asthmatic children. In further in vitro experiments on macrophages treated with house dust mites, they demonstrated that TUG1 could regulate B7-H3 expression in macrophages by sponging miR-29c, which then controls Th2 differentiation, providing novel potential diagnostic biomarkers and therapeutic targets for asthma.…”

PCAT6 May Be a Whistler and Checkpoint Target for Precision Therapy in Human Cancers

“…They play different regulatory roles by serving as different functional molecules, such as signals, decoys, guides, and scaffolds in multiple tumor cellular processes [ 22 , 72 ]. In recent studies, mounting evidence indicates that the lncRNA-miRNA-mRNA axis is present in cancers [ 73 , 74 , 75 , 76 , 77 ]. LncRNAs can mediate competitive mRNAs crosstalk by sharing microRNA response elements (MREs), which are also known as competing endogenous RNA (ceRNA) regulatory network mechanisms.…”