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MicroRNA-142-5p contributes to Hashimoto's thyroiditis by targeting CLDN1.
- Source :
-
Journal of translational medicine [J Transl Med] 2016 Jun 08; Vol. 14 (1), pp. 166. Date of Electronic Publication: 2016 Jun 08. - Publication Year :
- 2016
-
Abstract
- Background: 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).<br />Methods: 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.<br />Results: 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).<br />Conclusions: Our findings indicate a previously unrecognized mechanism that miR-142-5p, targeting CLDN1, plays an important role in HT pathogenesis.
- Subjects :
- Antibodies metabolism
Cell Membrane Permeability
Epithelium metabolism
Epithelium pathology
Fluorescent Antibody Technique
Gene Expression Profiling
Humans
In Situ Hybridization
MicroRNAs genetics
Oligonucleotide Array Sequence Analysis
Oligonucleotide Probes metabolism
Oligonucleotides metabolism
RNA, Messenger genetics
RNA, Messenger metabolism
Real-Time Polymerase Chain Reaction
Reproducibility of Results
Thyroglobulin immunology
Thyroid Epithelial Cells metabolism
Thyroid Epithelial Cells pathology
Thyroid Gland metabolism
Thyroid Gland pathology
Thyroiditis pathology
Claudin-1 metabolism
MicroRNAs metabolism
Thyroiditis genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1479-5876
- Volume :
- 14
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of translational medicine
- Publication Type :
- Academic Journal
- Accession number :
- 27277258
- Full Text :
- https://doi.org/10.1186/s12967-016-0917-6