MicroRNA-142-5p contributes to Hashimoto's thyroiditis by targeting CLDN1.
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).



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.



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).



Our findings indicate a previously unrecognized mechanism that miR-142-5p, targeting CLDN1, plays an important role in HT pathogenesis.
State Key Laboratory of Cancer Biology and Department of Pathology, Xijing Hospital, Fourth Military Medical University, Changle West Road #169, Xi'an, 710032, People's Republic of China.|Department of Clinical Laboratory, Lintong Sanatorium, Lanzhou Military Command, Xi'an, 710600, People's Republic of China.
Jin
J
Zhu
State Key Laboratory of Cancer Biology and Department of Pathology, Xijing Hospital, Fourth Military Medical University, Changle West Road #169, Xi'an, 710032, People's Republic of China.|Department of Pathology, Foshan First People's Hospital, Foshan, 528000, People's Republic of China.
Yuehua
Y
Zhang
State Key Laboratory of Cancer Biology and Department of Pathology, Xijing Hospital, Fourth Military Medical University, Changle West Road #169, Xi'an, 710032, People's Republic of China.
Weichen
W
Zhang
The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, People's Republic of China.
Wei
W
Zhang
State Key Laboratory of Cancer Biology and Department of Pathology, Xijing Hospital, Fourth Military Medical University, Changle West Road #169, Xi'an, 710032, People's Republic of China.
Linni
L
Fan
State Key Laboratory of Cancer Biology and Department of Pathology, Xijing Hospital, Fourth Military Medical University, Changle West Road #169, Xi'an, 710032, People's Republic of China.
Lu
L
Wang
State Key Laboratory of Cancer Biology and Department of Pathology, Xijing Hospital, Fourth Military Medical University, Changle West Road #169, Xi'an, 710032, People's Republic of China.
Yixiong
Y
Liu
Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, People's Republic of China.
Shasha
S
Liu
State Key Laboratory of Cancer Biology and Department of Pathology, Xijing Hospital, Fourth Military Medical University, Changle West Road #169, Xi'an, 710032, People's Republic of China.
Ying
Y
Guo
State Key Laboratory of Cancer Biology and Department of Pathology, Xijing Hospital, Fourth Military Medical University, Changle West Road #169, Xi'an, 710032, People's Republic of China.
Yingmei
Y
Wang
Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
Jun
J
Yi
State Key Laboratory of Cancer Biology and Department of Pathology, Xijing Hospital, Fourth Military Medical University, Changle West Road #169, Xi'an, 710032, People's Republic of China. yanqingguo163@163.com.
Qingguo
Q
Yan
State Key Laboratory of Cancer Biology and Department of Pathology, Xijing Hospital, Fourth Military Medical University, Changle West Road #169, Xi'an, 710032, People's Republic of China. zhwang@fmmu.edu.cn.
Zhe
Z
Wang
State Key Laboratory of Cancer Biology and Department of Pathology, Xijing Hospital, Fourth Military Medical University, Changle West Road #169, Xi'an, 710032, People's Republic of China. gaosheng_huang@hotmail.com.
Gaosheng
G
Huang
D000906:Antibodies / Q000378:metabolism; D002463:Cell Membrane Permeability; D062445:Claudin-1 / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D006801:Humans; D017403:In Situ Hybridization; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D015345:Oligonucleotide Probes / Q000378:metabolism; D009841:Oligonucleotides / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D013954:Thyroglobulin / Q000276:immunology; D000072637:Thyroid Epithelial Cells / Q000378:metabolism / Q000473:pathology; D013961:Thyroid Gland / Q000378:metabolism / Q000473:pathology; D013966:Thyroiditis / Q000235:genetics* / Q000473:pathology
D000906:Antibodies; C568108:CLDN1 protein, human; D062445:Claudin-1; C555159:MIRN142 microRNA, human; D035683:MicroRNAs; D015345:Oligonucleotide Probes; D009841:Oligonucleotides; D012333:RNA, Messenger; C477371:locked nucleic acid; D013954:Thyroglobulin
Autoimmune diseases; CLDN1; Hashimoto’s thyroiditis; miR-142-5p; miRNA