CONTEXT: Graves' disease (GD) is a common autoimmune disease that affects the thyroid gland. As a new class of modulators of gene expression, microRNA (miRNA) have been reported to play a vital role in immune functions and in the development of autoimmunity and autoimmune disease. OBJECTIVE: This study sought to characterize the different miRNA expression in peripheral blood mononuclear cells (PBMC) from GD patients and healthy individuals and examine their direct responses to T(3) treatment. METHODS: Forty-one patients who met criteria for initial GD, 13 GD patients in remission, and 35 healthy controls were recruited. Microarray was used to analyze the expression patterns of miRNA in PBMC obtained from initial GD patients and healthy controls. Three top-ranked miRNA were selected and validated by TaqMan-based real-time PCR in healthy controls, initial GD patients, and GD patients in remission. Furthermore, we cultured PBMC from healthy donors with or without T(3) treatment to examine direct effects of T(3) on selective miRNA. RESULTS: There were sixteen miRNA expressed differently in PBMC from initial GD patients compared with normal subjects. Further analysis consistently showed that the expression of miR-154*, miR-376b, and miR-431* were suppressed in PBMC from initial GD patients. In addition, their expression levels were recovered in GD patients in remission. Meanwhile, T(3) treatment could directly inhibit the expression of these miRNA in cultured PBMC from healthy subjects. CONCLUSIONS: The present work revealed that differentially expressed miRNA were associated with GD and T(3) exposure, which might serve as novel biomarkers of GD and potential targets for GD treatment.
CONTEXT: Graves' disease (GD) is a common autoimmune disease that affects the thyroid gland. As a new class of modulators of gene expression, microRNA (miRNA) have been reported to play a vital role in immune functions and in the development of autoimmunity and autoimmune disease. OBJECTIVE: This study sought to characterize the different miRNA expression in peripheral blood mononuclear cells (PBMC) from GDpatients and healthy individuals and examine their direct responses to T(3) treatment. METHODS: Forty-one patients who met criteria for initial GD, 13 GDpatients in remission, and 35 healthy controls were recruited. Microarray was used to analyze the expression patterns of miRNA in PBMC obtained from initial GDpatients and healthy controls. Three top-ranked miRNA were selected and validated by TaqMan-based real-time PCR in healthy controls, initial GDpatients, and GDpatients in remission. Furthermore, we cultured PBMC from healthy donors with or without T(3) treatment to examine direct effects of T(3) on selective miRNA. RESULTS: There were sixteen miRNA expressed differently in PBMC from initial GDpatients compared with normal subjects. Further analysis consistently showed that the expression of miR-154*, miR-376b, and miR-431* were suppressed in PBMC from initial GDpatients. In addition, their expression levels were recovered in GDpatients in remission. Meanwhile, T(3) treatment could directly inhibit the expression of these miRNA in cultured PBMC from healthy subjects. CONCLUSIONS: The present work revealed that differentially expressed miRNA were associated with GD and T(3) exposure, which might serve as novel biomarkers of GD and potential targets for GD treatment.
Authors: Julia Kovacova; Jaroslav Juracek; Alexandr Poprach; Jindrich Kopecky; Ondrej Fiala; Marek Svoboda; Pavel Fabian; Lenka Radova; Petr Brabec; Tomas Buchler; Ondrej Slaby Journal: Cancer Genomics Proteomics Date: 2019 Sep-Oct Impact factor: 4.069