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Comprehensive Analysis of lncRNA Expression Profile and the Potential Role of ENST00000604491 in Graves' Disease

BACKGROUND: Graves' disease (GD) is one of the most common autoimmune diseases worldwide and develops in 20 to 50 cases per 100,000 persons annually. Long noncoding RNAs (lncRNAs) are widely expressed in multiple human diseases and have pivotal functions in gene regulation. This study is aimed...

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Autores principales: Liu, Yingzhao, Zou, Junli, Xu, Juan, Wang, Xuehua, Xing, Jie, Wang, Li, Peng, Huiyong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9061081/
https://www.ncbi.nlm.nih.gov/pubmed/35509980
http://dx.doi.org/10.1155/2022/8067464
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author Liu, Yingzhao
Zou, Junli
Xu, Juan
Wang, Xuehua
Xing, Jie
Wang, Li
Peng, Huiyong
author_facet Liu, Yingzhao
Zou, Junli
Xu, Juan
Wang, Xuehua
Xing, Jie
Wang, Li
Peng, Huiyong
author_sort Liu, Yingzhao
collection PubMed
description BACKGROUND: Graves' disease (GD) is one of the most common autoimmune diseases worldwide and develops in 20 to 50 cases per 100,000 persons annually. Long noncoding RNAs (lncRNAs) are widely expressed in multiple human diseases and have pivotal functions in gene regulation. This study is aimed at determining the lncRNA profile in peripheral blood mononuclear cells (PBMCs) from GD patients and investigating the role of ENST00000604491 in GD. METHODS: A total of 31 GD patients and 32 normal controls were enrolled in the study. Next-generation sequencing was performed to identify the dysregulated lncRNAs in the PBMCs from the 5 GD patients and 5 normal controls, and 26 GD patients and 27 controls were used to verify the selected lncRNAs. The relative expression of verified lncRNAs, forkhead box P1 (FOXP1), and IKAROS family zinc finger 3 (IKZF3) from these samples was detected by quantitative real-time PCR. The potential biomarker value was assessed by using receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 37,683 dysregulated expressed lncRNAs were indicated, of which 5 lncRNAs were significantly upregulated and 83 lncRNAs were remarkably downregulated in the GD patients compared with healthy subjects. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that abnormally expressed lncRNAs were mainly enriched in immune system-related signalling pathways. Among the selected lncRNAs, the relative expression of ENST00000604491 was significantly downregulated and negatively correlated with the serum levels of thyroid-stimulating hormone receptor antibodies (TRAb) in GD patients. Further studies confirmed that decreased FOXP1 expression was inversely correlated with serum TRAb levels in GD patients. Moreover, there was a notably positive correlation between ENST00000604491 expression and FOXP1 transcript levels in GD. The area under the ROC curve of ENST00000604491 was up to 0.74 (95% confidence interval: 0.60-0.87, p < 0.01), and the sensitivity and specificity were 53.85% and 88.89%, respectively. CONCLUSION: The present study identifies ENST00000604491 as a significantly attenuated lncRNA in GD patients, which may contribute to the pathogenesis of GD by regulating FOXP1 and represent a potential biomarker for GD.
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spelling pubmed-90610812022-05-03 Comprehensive Analysis of lncRNA Expression Profile and the Potential Role of ENST00000604491 in Graves' Disease Liu, Yingzhao Zou, Junli Xu, Juan Wang, Xuehua Xing, Jie Wang, Li Peng, Huiyong J Immunol Res Research Article BACKGROUND: Graves' disease (GD) is one of the most common autoimmune diseases worldwide and develops in 20 to 50 cases per 100,000 persons annually. Long noncoding RNAs (lncRNAs) are widely expressed in multiple human diseases and have pivotal functions in gene regulation. This study is aimed at determining the lncRNA profile in peripheral blood mononuclear cells (PBMCs) from GD patients and investigating the role of ENST00000604491 in GD. METHODS: A total of 31 GD patients and 32 normal controls were enrolled in the study. Next-generation sequencing was performed to identify the dysregulated lncRNAs in the PBMCs from the 5 GD patients and 5 normal controls, and 26 GD patients and 27 controls were used to verify the selected lncRNAs. The relative expression of verified lncRNAs, forkhead box P1 (FOXP1), and IKAROS family zinc finger 3 (IKZF3) from these samples was detected by quantitative real-time PCR. The potential biomarker value was assessed by using receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 37,683 dysregulated expressed lncRNAs were indicated, of which 5 lncRNAs were significantly upregulated and 83 lncRNAs were remarkably downregulated in the GD patients compared with healthy subjects. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that abnormally expressed lncRNAs were mainly enriched in immune system-related signalling pathways. Among the selected lncRNAs, the relative expression of ENST00000604491 was significantly downregulated and negatively correlated with the serum levels of thyroid-stimulating hormone receptor antibodies (TRAb) in GD patients. Further studies confirmed that decreased FOXP1 expression was inversely correlated with serum TRAb levels in GD patients. Moreover, there was a notably positive correlation between ENST00000604491 expression and FOXP1 transcript levels in GD. The area under the ROC curve of ENST00000604491 was up to 0.74 (95% confidence interval: 0.60-0.87, p < 0.01), and the sensitivity and specificity were 53.85% and 88.89%, respectively. CONCLUSION: The present study identifies ENST00000604491 as a significantly attenuated lncRNA in GD patients, which may contribute to the pathogenesis of GD by regulating FOXP1 and represent a potential biomarker for GD. Hindawi 2022-04-25 /pmc/articles/PMC9061081/ /pubmed/35509980 http://dx.doi.org/10.1155/2022/8067464 Text en Copyright © 2022 Yingzhao Liu et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Liu, Yingzhao
Zou, Junli
Xu, Juan
Wang, Xuehua
Xing, Jie
Wang, Li
Peng, Huiyong
Comprehensive Analysis of lncRNA Expression Profile and the Potential Role of ENST00000604491 in Graves' Disease
title Comprehensive Analysis of lncRNA Expression Profile and the Potential Role of ENST00000604491 in Graves' Disease
title_full Comprehensive Analysis of lncRNA Expression Profile and the Potential Role of ENST00000604491 in Graves' Disease
title_fullStr Comprehensive Analysis of lncRNA Expression Profile and the Potential Role of ENST00000604491 in Graves' Disease
title_full_unstemmed Comprehensive Analysis of lncRNA Expression Profile and the Potential Role of ENST00000604491 in Graves' Disease
title_short Comprehensive Analysis of lncRNA Expression Profile and the Potential Role of ENST00000604491 in Graves' Disease
title_sort comprehensive analysis of lncrna expression profile and the potential role of enst00000604491 in graves' disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9061081/
https://www.ncbi.nlm.nih.gov/pubmed/35509980
http://dx.doi.org/10.1155/2022/8067464
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