Background: Graves' disease is a common autoimmune disease. Cytokines and their signalling pathways play a major part in the pathogenesis of Graves' disease; however, the underlying mechanism needs to be clarified. Aims: The aim of this study was to explore whether circular RNAs participate 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 total 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 cytometry and CCK8 assays were used to detect the apoptotic and proliferative levels of Jurkat cells (T lymphocytes) with the silenced expression of circRNA. ELISA was performed to detect the growth and apoptosis-related proteins. The competition mechanism of endogenous RNA was explored by real-time fluorescence qPCR. Results: A total of 366 significantly differentially expressed circular RNAs were identified in the Graves' disease group compared to healthy controls. The level of hsa_circ_0090364 was elevated in Graves' disease patients and positively 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 mechanisms of Graves' disease and potential targets for drug treatment.
Background: Graves' disease is a common autoimmune disease. Cytokines and their signalling pathways play a major part in the pathogenesis of Graves' disease; however, the underlying mechanism needs to be clarified. Aims: The aim of this study was to explore whether circular RNAs participate 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 total 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 cytometry and CCK8 assays were used to detect the apoptotic and proliferative levels of Jurkat cells (T lymphocytes) with the silenced expression of circRNA. ELISA was performed to detect the growth and apoptosis-related proteins. The competition mechanism of endogenous RNA was explored by real-time fluorescence qPCR. Results: A total of 366 significantly differentially expressed circular RNAs were identified in the Graves' disease group compared to healthy controls. The level of hsa_circ_0090364 was elevated in Graves' disease patients and positively 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 mechanisms of Graves' disease and potential targets for drug treatment.
Authors: L Bartalena; E Masiello; F Magri; G Veronesi; E Bianconi; F Zerbini; M Gaiti; E Spreafico; D Gallo; P Premoli; E Piantanida; M L Tanda; M Ferrario; P Vitti; L Chiovato Journal: J Endocrinol Invest Date: 2016-07-27 Impact factor: 4.256