Identification of lncRNA and mRNA Expression Profile in Relapsed Graves' Disease.

Qiuming Yao,Xi Jia,Ronghua Song,Zhenyu Song,Jinan Zhang,Bin Wang

doi:10.3389/fcell.2021.756560

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.

Highlights

Graves’ disease, known as toxic diffuse goiter, is characterized by the production of antibodies against thyroid stimulating hormone receptors (TRAb), leading to the hypertrophy and hyperfunction of the thyroid follicular cells (Morshed et al, 2012)
To explore the crucial role of Long non-coding RNAs (lncRNAs) and mRNAs associated with the recurrence and development of Graves’ disease (GD), we performed RNA-Seq to detect the expression profile of lncRNAs and mRNAs in GD and normal healthy controls (NC)
We found that 1336 lncRNAs and 266 mRNAs were significantly differentially expressed between relapsed GD patients and healthy controls

Summary

Introduction

Graves’ disease, known as toxic diffuse goiter, is characterized by the production of antibodies against thyroid stimulating hormone receptors (TRAb), leading to the hypertrophy and hyperfunction of the thyroid follicular cells (Morshed et al, 2012). There are three main treatment methods for GD, including anti-thyroid drugs, radioactive iodine (RAI), and surgical resection. Compared with RAI and surgery, the disadvantage of antithyroid drugs mainly includes lower remission rate of hyperthyroidism and higher recurrence rate of patients with high TRAb titer. Anti-thyroid drugs can cause side effects such as skin rash, joint pain, agranulocytosis, and liver toxicity (Kotwal et al, 2018). RAI is contraindicated in pregnant and lactating women and patients with active thyroid eye disease (Kotwal et al, 2018). Surgical removal of the thyroid can quickly improve the symptoms of hyperthyroidism, patients need to take thyroid hormones throughout their lives, and the operation itself can cause a variety of complications such as hypoparathyroidism, recurrent laryngeal nerve injury, and neck hematoma. The purpose of this study is to identify lncRNA and mRNA expression profile in relapsed Graves’ disease

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