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Endocrine

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26.05.2023 | Original Article

MicroRNA-376b is involved in the pathogenesis of thyroid-associated ophthalmopathy by regulating HAS2

verfasst von: Rongjiao Liu, Zhengqin Ye, Qi Liu, Miao Xuan, Ran Li, Liya Zhang, Keqin Zhang, Ping Fang, Ying Xue

Erschienen in: Endocrine | Ausgabe 1/2023

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Abstract

Purpose

The aim of this study was to investigate the microRNA (miRNA) expression profile in peripheral blood mononuclear cells (PBMC) of thyroid-associated ophthalmopathy (TAO) patients and to explore the molecular mechanisms of MicroRNA-376b (miR-376b) in the pathogenesis of TAO.

Methods

PBMCs from TAO patients and healthy controls were analyzed by miRNA microarray to screen for the significantly differentially expressed miRNAs. The miR-376b expression in PBMCs were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). The downstream target of miR-376b was screened by online bioinformatics, and detected by qRT-PCR and Western blotting.

Results

Compared with normal controls, 26 miRNAs were significantly different in PBMCs of TAO patients (14 miRNAs were down-regulated and 12 miRNAs were up-regulated). Among them, miR-376b expression was significantly decreased in PBMCs from TAO patients compared to healthy controls. Spearman correlation analysis revealed that miR-376b expression in PBMCs was significantly negatively correlated with free triiodothyronine (FT3), and positively correlated with thyroid-stimulating hormone (TSH). MiR-376b expression was obviously reduced in 6T-CEM cells after triiodothyronine (T3) stimulation compared to controls. MiR-376b mimics significantly decreased hyaluronan synthase 2 (HAS2) protein expression and the mRNA expression of intercellular cell adhesion molecule-1 (ICAM1) and tumor necrosis factor-α (TNF-α) in 6T-CEM cells, whereas miR-376b inhibitors markedly elevated HAS2 protein expression and gene expression of ICAM1 and TNF-α.

Conclusions

MiR-376b expression in PBMCs was significantly decreased in PBMCs from TAO patients compared with the healthy controls. MiR-376b, regulated by T3, could modulate the expression of HAS2 and inflammatory factors. We speculate that miR-376b may be involved in the pathogenesis of TAO patients by regulating the expression of HAS2 and inflammatory factors.

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Titel: MicroRNA-376b is involved in the pathogenesis of thyroid-associated ophthalmopathy by regulating HAS2
verfasst von: Rongjiao Liu
Zhengqin Ye
Qi Liu
Miao Xuan
Ran Li
Liya Zhang
Keqin Zhang
Ping Fang
Ying Xue
Publikationsdatum: 26.05.2023
Verlag: Springer US
Erschienen in: Endocrine / Ausgabe 1/2023
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI: https://doi.org/10.1007/s12020-023-03382-y

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MicroRNA-376b is involved in the pathogenesis of thyroid-associated ophthalmopathy by regulating HAS2