MicroRNA-142-5p contributes to Hashimoto’s thyroiditis by targeting CLDN1

Journal of Translational Medicine

Research

Shasha Liu¹  Jun Yi²  Yingmei Wang³  Linni Fan³  Weichen Zhang³  Ying Guo³  Zhe Wang³  Gaosheng Huang³  Lu Wang³  Yixiong Liu³  Qingguo Yan³  Jin Zhu⁴  Yuehua Zhang⁵  Wei Zhang⁶ 

[1] Department of Neurology, Tangdu Hospital, Fourth Military Medical University, 710038, Xi’an, People’s Republic of China;Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, 710032, Xi’an, People’s Republic of China;State Key Laboratory of Cancer Biology and Department of Pathology, Xijing Hospital, Fourth Military Medical University, Changle West Road #169, 710032, Xi’an, People’s Republic of China;State Key Laboratory of Cancer Biology and Department of Pathology, Xijing Hospital, Fourth Military Medical University, Changle West Road #169, 710032, Xi’an, People’s Republic of China;Department of Clinical Laboratory, Lintong Sanatorium, Lanzhou Military Command, 710600, Xi’an, People’s Republic of China;State Key Laboratory of Cancer Biology and Department of Pathology, Xijing Hospital, Fourth Military Medical University, Changle West Road #169, 710032, Xi’an, People’s Republic of China;Department of Pathology, Foshan First People’s Hospital, 528000, Foshan, People’s Republic of China;The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, Fourth Military Medical University, 710038, Xi’an, People’s Republic of China;

关键词: Autoimmune diseases;    Hashimoto’s thyroiditis;    miRNA;    miR-142-5p;    CLDN1;   

DOI  :  10.1186/s12967-016-0917-6

 received in 2016-03-01, accepted in 2016-05-20,  发布年份 2016

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© The Author(s) 2016