Circular RNA profile in Graves’ disease and potential function of hsa_circ_0090364

Abstract

Background: Graves’ disease is a common autoimmune disease. Cytokines and their signalling pathways play a major part in the pathogenesis of Gr aves’ disease; however, the underlying mechanism needs to be clarified. Aims: The aim of this study was to explore whether circular RNAs par ticipate in the immunological pathology of Graves’ disease via cytokine-related signalling pathways. Methods: Bioinformatics analysis was performed to identify differentially expressed circular RNAs and their targets and associated pathways. A tota l of three patients with Graves’ disease and three sex- and age-matched healthy controls were enrolled for validation with microarray analysis and real-time quantitative PCR (qPCR). An additional 24 patients with Graves’ disease and 24 gender- and age-matched controls were included for validation by real-time fluorescent qPCR. Flow cyto metry and CCK8 assays were used to detect the apoptotic and proliferative levels of J urkat cells (T lymphocytes) with the silenced expression of circRNA. ELISA was performed to detect the growth and apoptosis-related proteins. The competition mechanism of en dogenous RNA was explored by real-time fluorescence qPCR. Results: A total of 366 significantly differentially expressed circular RN As were identified in the Graves’ disease group compared to healthy cont rols. The level of hsa_circ_0090364 was elevated in Graves’ disease patients and p ositively correlated with thyroid-stimulating hormone receptor antibodies. Further analyses suggested that hsa_ circ_0090364 may regulate the JAK-STAT pathway via the hsa-miR- 378a-3p/IL-6ST/IL21R axis to promote cell growth. Conclusions: These results provide novel clues into the pathophysiological m echanisms of Graves’ disease and potential targets for drug treatment.

Keywords

• bioinformatics analysis
• circular rnas
• graves’ disease
• hsa_circ_0090364