Identification of lncRNA and mRNA Expression Profile in Relapsed Graves’ Disease

Abstract

Background: Graves’ disease (GD) is a common autoimmune disease, and its pathogenesis is unclear. Studies have found that the occurrence of GD is related to the immune disorder caused by the interaction of genetic susceptibility and environmental factors. The CD4+ T cell subset is closely related to the immune disorder of GD. LncRNAs are RNA molecules with a length of more than 200 nt and are involved in a variety of autoimmune diseases. However, the roles of lncRNAs in recurrent GD are still elusive. The purpose of this study is to identify lncRNA and mRNA expression profile in relapsed Graves’ disease.Method: CD4+ T cells from 12 recurrent GD and 8 healthy controls were collected for high-throughput sequencing. The gene-weighted co-expression network analysis (WGCNA) was used to construct the co-expression module relevant to recurrent GD, and the key genes in the module were verified by RT-PCR.Results: There are 602 upregulated lncRNAs and 734 downregulated lncRNAs in CD4+ T cells in recurrent GD patients compared with the healthy controls. The module most relevant to GD recurrence was constructed using WGCNA, and the key genes in the module were verified by RT-PCR. We found that the expression of RPL8, OAS2, NFAT5, DROSHA, NONHSAT093153.2, NONHSAT118924.2, and NONHSAT209004.1 was significantly decreased in GD group (p < 0.001, p < 0.001, p < 0.01, p < 0.05, p < 0.001, p < 0.05, and p < 0.01, respectively).Conclusion: LncRNAs are closely related to the recurrence of GD. For the first time, we constructed the expression profile of lncRNAs and mRNAs in CD4+ T cells in recurrent GD patients.

Identification of potential immunotherapeutic targets and prognostic biomarkers in Graves' disease using weighted gene co-expression network analysis

“… a Functional enrichment analysis was performed with an integrative method that discovers significantly enriched pathways, across multiple datasets such as DisGeNET [ 22 ], Clinical Variations [ 24 ], DisGeNET [ 25 ], BeFree [ 26 ], BioCyc [ 27 ], KEGG [ 28 ], and MSigDBBioCarta [ 30 ]. …”

“…To gain insights into the biological processes and molecular functions related to the targeted immune hubs in glioma, several analyses were conducted using multiple datasets such as DisGeNET [ 32 ], Clinical Variations [ 24 ], DisGeNET [ 25 ], BeFree [ 26 ], BioCyc [ 27 ], KEGG [ 28 ], and MSigDBBioCarta [ 30 ]. ToppGene and the clusterProfiler package were used to perform GO analysis and KEGG analysis to uncover enriched pathways across multiple datasets [ [33] , [34] , [35] ].…”

“…The initial triggers for autoantibody production and immune activation are still unknown, and the precise interactions between immune cells and autoantibodies in the thyroid gland require further investigation [ 12 , 16 ]. However, recent advances in computational tools, such as the immunogenicity-potential scoring (IPS) [ 17 , 18 ], microenvironment cell populations-counter (MCP) [ [19] , [20] , [21] ], X-cells algorithms [ 22 , 23 ], and weighted gene co-expression network analysis (WGCNA) [ 24 , 25 ], have enabled researchers to gain a deeper understanding of the molecular mechanisms underlying autoantibody production and the complex interactions between stromal and immune cells in the thyroid gland [ 26 , 27 ]. These cutting-edge tools allow for large-scale gene expression analysis to identify key biological pathways and processes involved in the path immunology of autoimmune disorders, providing valuable insights into the underlying mechanisms of these diseases [ 28 ].…”

Comprehensive Analysis of lncRNA Expression Profile and the Potential Role of ENST00000604491 in Graves’ Disease

“…Jiang et al found that n335641, n337845, and TCONS_00022357-XLOC_010919 may participate in the proliferation and survival of B cells in GD [ 21 ]. Yao et al focused on relapsed GD patients and found that three downregulated lncRNAs (NONHSAT093153.2, NONHSAT118924.2, and NONHSAT209004.1) were closely related to the recurrence of GD [ 15 ]. In the present study, we found a signature profile of numerous dysregulated lncRNAs (27,354 upregulated lncRNAs and 10,329 downregulated lncRNAs) in PBMCs from GD patients compared with normal controls by sequencing technology.…”

“…Evidence has suggested that many lncRNAs are involved in the pathogenesis of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, and Hashimoto's thyroiditis [ 12 – 14 ]. Although the lncRNA profiles in CD4 + T cells of relapsed GD have been preliminarily investigated [ 15 , 16 ], the dysregulated lncRNAs in peripheral blood mononuclear cells (PBMCs) from GD patients and their potential functions remain poorly understood. Here, the present study is aimed at investigating the potential roles of lncRNAs in PBMCs from patients with GD.…”