Identification of putative miRNA biomarkers in early rheumatoid arthritis by genome-wide microarray profiling: A pilot study
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Accepted version
Author(s)
Type
Journal Article
Abstract
Despite the existing research, the etiology of rheumatoid arthritis (RA), an autoimmune disease remains poorly understood with early and accurate diagnosis difficult to achieve. MicroRNAs (miRNAs) play an important role in biological processes as modulators of transcription and translation. Previous studies have demonstrated a downregulation of several genes in early RA stages and in addition, miRNAs may serve as early biomarkers of subclinical changes in early RA.
When comparing the four groups (ANOVA P < 0.01, fold change > 4), we found 253 differentially expressed miRNAs. Of these, 97 miRNAs were identified as overexpressed in early rheumatoid arthritis. The validation of miRNA microarray expression was performed in a set by RT-qPCR and showed strong agreement with microarray expression data. The putative targets of overexpressed microRNAs in early RA were significantly enriched in apoptosis, tolerance loss and Wnt pathways. Moreover, ROC analysis showed values of AUC 0.76 and P < 0.05 for miR361-5p, identifying this miRNA as a potential biomarker of disease.
We identified specific microRNAs associated with early rheumatoid arthritis and proposed them as early biomarkers of disease. Our results provide novel insight into immune disease physiopathology and describe unreported microRNAs in RA with potential for clinical use.
When comparing the four groups (ANOVA P < 0.01, fold change > 4), we found 253 differentially expressed miRNAs. Of these, 97 miRNAs were identified as overexpressed in early rheumatoid arthritis. The validation of miRNA microarray expression was performed in a set by RT-qPCR and showed strong agreement with microarray expression data. The putative targets of overexpressed microRNAs in early RA were significantly enriched in apoptosis, tolerance loss and Wnt pathways. Moreover, ROC analysis showed values of AUC 0.76 and P < 0.05 for miR361-5p, identifying this miRNA as a potential biomarker of disease.
We identified specific microRNAs associated with early rheumatoid arthritis and proposed them as early biomarkers of disease. Our results provide novel insight into immune disease physiopathology and describe unreported microRNAs in RA with potential for clinical use.
Date Issued
2019-12-15
Date Acceptance
2019-08-26
Citation
Gene, 2019, 720
ISSN
0378-1119
Publisher
Elsevier BV
Journal / Book Title
Gene
Volume
720
Copyright Statement
© 2019 Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/
Sponsor
Medical Research Council (MRC)
Medical Research Council (MRC)
Medical Research Council
Identifier
https://www.sciencedirect.com/science/article/pii/S0378111919307401?via%3Dihub
Grant Number
MR/L01632X/1
MR/L01632X/1
MEDBIO UK
Subjects
Biomarker
CCP
Early rheumatoid arthritis
Microarray expression
miRNA
Adult
Arthritis, Rheumatoid
Biomarkers
Case-Control Studies
Female
Gene Expression Profiling
Genome, Human
Humans
Male
MicroRNAs
Middle Aged
Pilot Projects
ROC Curve
Developmental Biology
0604 Genetics
Publication Status
Published online
Article Number
144081
Date Publish Online
2019-08-29