LncRNA‐miRNA network analysis across the Th17 cell line reveals biomarker potency of lncRNA NEAT1 and KCNQ1OT1 in multiple sclerosis

Abstract

Differentiation of CD4+ T cells into Th17 cells is an important factor in the onset and progression of multiple sclerosis (MS) and Th17/Treg imbalance. Little is known about the role of lncRNAs in the differentiation of CD4+ cells from Th17 cells. This study aimed to analyse the lncRNA‐miRNAs network involved in MS disease and its role in the differentiation of Th17 cells. The lncRNAs in Th17 differentiation were obtained from GSE66261 using the GEO datasets. Differential expression of lncRNAs in Th17 primary cells compared to Th17 effector cells was investigated by RNA‐seq analysis. Next, the most highlighted lncRNAs in autoimmune diseases were downloaded from the lncRNAs disease database, and the most critical miRNA was extracted by literature search. Then, the lncRNA‐miRNA interaction was achieved by the Starbase database, and the ceRNA network was designed by Cytoscape. Finally, using the CytoHubba application, two hub lncRNAs with the most interactions with miRNAs were identified by the MCODE plug‐in. The expression level of genes was measured by qPCR, and the plasma level of cytokines was analysed by ELISA kits. The results showed an increase in the expression of NEAT1, KCNQ1OT1 and RORC and a decrease in the expression of FOXP3. In plasma, an upregulation of IL17 and a downregulation of TGFB inflammatory cytokines were detected. The dysregulated expression of these genes could be attributed to relapsing‐remitting MS (RR‐MS) patients and help us understand MS pathogenesis better.

Integrated Analysis of Immune Infiltration and Hub Pyroptosis-Related Genes for Multiple Sclerosis

“…To screen out and unveil a systematic regulatory network of the pyroptosis-related CASP4 and NRLC4 in MS, we carried out a literature review to identify lncRNAs and miRNAs in MS. Among the target lncRNAs obtained from the database, four lncRNAs, namely KCNQ1OT1, 61 NEAT, 61 , 62 1OIP5-AS1 63 and XIST, 64 were reportedly upregulated in MS. Furthermore, six miRNAs among the target miRNAs of CASP4 and NRLC4 were shown to be downregulated in MS: hsa-let-7d-5p, hsa-mir-103a-3p, hsa-mir-122-5p, hsa-mir-210-3p, hsa-mir-335-5p, and hsa-mir-671-5p.…”

MAPK Is a Mutual Pathway Targeted by Anxiety-Related miRNAs, and E2F5 Is a Putative Target for Anxiolytic miRNAs

“…Common target genes among either anxiolytic or anxiogenic highlighted miR are determined via the miRDB database, and their potential protein-protein interaction (PPI) network and key hub genes were constructed using the STRING database version 11.0 ( , accessed on 18 July 2022) with confidence scores of ≥0.9 as a threshold [ 13 , 14 ]. Moreover, specific interactions of each highlighted miR with the mRNA sequence of common target genes were also predicted by the TargetScan database to confirm better the possibility of miR-mRNA interactions ( , accessed on 21 August 2022) [ 15 , 16 ]. Besides, the interaction of common target proteins of higher rank with other cellular proteins was predicted by the Pathway Commons database ( , accessed on 5 September 2022) [ 17 ].…”

Regulatory Effects of Long Non-coding RNAs on Th17/Treg Differentiation and Imbalance

“…38 Karimi et al noted that up-regulation of lncRNAs NEAT1 and KCNQ1OT1 was associated with Th17/Treg imbalance in patients with relapsing-remitting MS (RR-MS). 39 Line of evidence suggests that lnc-NEAT1 silencing in DCs promotes immune tolerance by increasing Tregs and decreasing the amount of Th17 cells, inhibiting T cell proliferation, and reducing inflammatory cell infiltration in experimental autoimmune myocarditis (EAM) and heart transplantation mouse models. 40 Figure 1 outlines some of the main lncRNAs influencing the Th17/Treg imbalance.…”