Circulating microRNA Expression Profiling Identifies miR-125a-5p Promoting T Helper 1 Cells Response in the Pathogenesis of Hashimoto's Thyroiditis
| Autor: | Li Wang, Xiangmei Ding, Shengjun Wang, Yingzhao Liu, Huiyong Peng, Xinyi Tang, Xuehua Wang, Si Xiong |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Adult Male lcsh:Immunologic diseases. Allergy Immunology Hashimoto Disease miR-125a-5p Biology Peripheral blood mononuclear cell Thyroiditis 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation microRNA T helper 1 cells medicine Immunology and Allergy Humans Circulating MicroRNA Original Research Aged Gene knockdown Gene Expression Profiling pathogenesis microRNA expression profiling Middle Aged Th1 Cells medicine.disease MAF Gene expression profiling MicroRNAs 030104 developmental biology Gene Expression Regulation Proto-Oncogene Proteins c-maf Cancer research biology.protein Female Antibody Transcriptome hashimoto's thyroiditis lcsh:RC581-607 030215 immunology |
| Zdroj: | Frontiers in Immunology, Vol 11 (2020) Frontiers in Immunology |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2020.01195/full |
| Popis: | MicroRNAs (miRNAs) have emerged as key regulators of cellular processes by suppressing target mRNAs at the posttranscriptional level. However, little is known regarding the expression of miRNAs in peripheral blood mononuclear cells (PBMCs) from Hashimoto's thyroiditis (HT) patients. Therefore, 38 HT patients and 36 healthy volunteers were enrolled in this study to identify HT-mediated changes in miRNA expression. Over 1,000 dysregulated miRNAs and their biological functions in the HT patients were identified. Among them, miR-125a-5p expression was upregulated and inversely correlated with low levels of MAF, a transcription factor that inhibits Th1 cells activity and the production of IFN-γ. Luciferase assay results demonstrated that MAF is a direct target gene of miR-125a-5p. Moreover, the proportion of circulating Th1 cells and the transcript levels of IFN-γ were increased in the HT patients. MiR-125a-5p expression positively correlated with the proportion of circulating Th1 cells and the serum concentrations of anti-thyroperoxidase antibodies in the HT patients. Interestingly, knockdown of miR-125a-5p in CD4+ T cells resulted in an elevated level of MAF but decreased the proportion of Th1 cells and the transcript level of IFN-γ in vitro. Furthermore, upregulated miR-125a-5p and IFN-γ transcript levels and downregulated MAF expression were detected in thyroid tissues from HT patients. Receiver operating characteristic (ROC) curves suggested that miR-125a-5p has a crucial role in the HT. Our results demonstrate that the elevated levels of miR-125a-5p contribute to the Th1 cells response in the HT patients and may be involved in the pathogenesis of HT. |
| Databáze: | OpenAIRE |
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