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- Title
MicroRNA-142-5p contributes to Hashimoto's thyroiditis by targeting CLDN1.
- Authors
Jin Zhu; Yuehua Zhang; Weichen Zhang; Wei Zhang; Linni Fan; Lu Wang; Yixiong Liu; Shasha Liu; Ying Guo; Yingmei Wang; Jun Yi; Qingguo Yan; Zhe Wang; Gaosheng Huang; Zhu, Jin; Zhang, Yuehua; Zhang, Weichen; Zhang, Wei; Fan, Linni; Wang, Lu
- Abstract
<bold>Background: </bold>MicroRNAs 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).<bold>Methods: </bold>MicroRNA 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.<bold>Results: </bold>Thirty-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).<bold>Conclusions: </bold>Our findings indicate a previously unrecognized mechanism that miR-142-5p, targeting CLDN1, plays an important role in HT pathogenesis.
- Subjects
MICRORNA; AUTOIMMUNE thyroiditis; GENE expression profiling; POLYMERASE chain reaction; IMMUNOHISTOCHEMISTRY; GENETICS; DIAGNOSIS; RNA metabolism; NUCLEOTIDE metabolism; CELL physiology; EPITHELIUM; FLUORESCENT antibody technique; GLOBULINS; IMMUNOGLOBULINS; IN situ hybridization; MEMBRANE proteins; NUCLEIC acid probes; RESEARCH evaluation; RNA; THYROID gland; THYROIDITIS; OLIGONUCLEOTIDE arrays
- Publication
Journal of Translational Medicine, 2016, Vol 14, p1
- ISSN
1479-5876
- Publication type
journal article
- DOI
10.1186/s12967-016-0917-6