Abstract
BackgroundMicroRNAs have the potential as diagnostic biomarkers and therapeutic targets in autoimmune diseases. However, very limited studies have evaluated the expression of microRNA profile in thyroid gland related to Hashimoto’s thyroiditis (HT).MethodsMicroRNA microarray expression profiling was performed and validated by quantitative RT-PCR. The expression pattern of miR-142-5p was detected using locked nucleic acid-in situ hybridization. The target gene was predicted and validated using miRNA targets prediction database, gene expression analysis, quantitative RT-PCR, western blot, and luciferase assay. The potential mechanisms of miR-142-5p were studied using immunohistochemistry, immunofluorescence, and quantitative assay of thyrocyte permeability.ResultsThirty-nine microRNAs were differentially expressed in HT (Fold change ≥2, P < 0.05) and miR-142-5p, miR-142-3p, and miR-146a were only high expression in HT thyroid gland (P < 0.001). miR-142-5p, which was expressed at high levels in injured follicular epithelial cells, was also detected in HT patient serum and positively correlated with thyroglobulin antibody (r ≥ 0.6, P < 0.05). Furthermore, luciferase assay demonstrated CLDN1 was the direct target gene of miR-142-5p (P < 0.05), and Immunohistochemical staining showed a reverse expression patterns with miR-142-5p and CLDN1. Overexpression of miR-142-5p in thyrocytes resulted in reducing of the expression of claudin-1 both in mRNA and protein level (P = 0.032 and P = 0.009 respectively) and increasing the permeability of thyrocytes monolayer (P < 0.01).ConclusionsOur findings indicate a previously unrecognized mechanism that miR-142-5p, targeting CLDN1, plays an important role in HT pathogenesis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0917-6) contains supplementary material, which is available to authorized users.
Highlights
MicroRNAs have the potential as diagnostic biomarkers and therapeutic targets in autoimmune diseases
Results miRNA expression profile of Hashimoto’s thyroiditis (HT) vs. normal thyroid To identify miRNA expression levels in the HT thyroid gland, we performed miRNA microarray analysis using RNA obtained from three primary HT cases, three HT component of HT associated with papillary thyroid carcinoma (PTC) cases, and three normal thyroid cases
Specific miRNA expression in HT associated with thyroglobulin antibody (TgAb) As the progress and diagnosis of HT depends mainly on detecting abnormal levels of serum markers, especially thyroid autoantibodies, we investigated the association of miR-142-5p, miR-142-3p, and miR-146a expression with clinical data
Summary
MicroRNAs have the potential as diagnostic biomarkers and therapeutic targets in autoimmune diseases. Very limited studies have evaluated the expression of microRNA profile in thyroid gland related to Hashimoto’s thyroiditis (HT). Hashimoto’s thyroiditis (HT) was first described by the Japanese physician Hakaru Hashimoto in 1912 [1]. Thereafter it was recognized as the first and most common organ-specific autoimmune disease in the world, and its prevalence has increased in recent years [2]. Accumulating data suggest that miRNAs are differentially expressed in autoimmune diseases and miRNA regulation may impact their development or prevention [4], including rheumatoid arthritis, systemic lupus erythematosus, primary Sjögren’s syndrome, multiple sclerosis, ulcerative colitis, and inflammatory bowel disease. The research on HT-related miRNAs is very limited, and not direct study on thyroid gland. We are afraid that maybe the results were not representative to some degree quite probably because of the uneven distribution of the characteristic lesions obtained from fine-needle aspiration biopsies and the limitations due to their limited candidate miRNAs and the small sample size
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