- Title
- Erythrocyte microRNA sequencing reveals differential expression in relapsing-remitting multiple sclerosis
- Creator
- Groen, Kira; Maltby, Vicki E.; Lea, Rodney A.; Sanders, Katherine A.; Fink, J. Lynn; Scott, Rodney J.; Tajouri, Lotti; Lechner-Scott, Jeannette
- Relation
- BMC Medical Genomics Vol. 11, no. 48
- Publisher Link
- http://dx.doi.org/10.1186/s12920-018-0365-7
- Publisher
- BioMed Central
- Resource Type
- journal article
- Date
- 2018
- Description
- Background: There is a paucity of knowledge concerning erythrocytes in the aetiology of Multiple Sclerosis (MS) despite their potential to contribute to disease through impaired antioxidant capacity and altered haemorheological features. Several studies have identified an abundance of erythrocyte miRNAs and variable profiles associated with disease states, such as sickle cell disease and malaria. The aim of this study was to compare the erythrocyte miRNA profile of relapsing-remitting MS (RRMS) patients to healthy sex- and age-matched controls. Methods: Erythrocytes were purified by density-gradient centrifugation and RNA was extracted. Following library preparation, samples were run on a HiSeq4000 Illumina instrument (paired-end 100 bp sequencing). Sequenced erythrocyte miRNA profiles (9 patients and 9 controls) were analysed by DESeq2. Differentially expressed miRNAs were validated by RT-qPCR using miR-152-3p as an endogenous control and replicated in a larger cohort (20 patients and 18 controls). After logarithmic transformation, differential expression was determined by two-tailed unpaired t-tests. Logistic regression analysis was carried out and receiver operating characteristic (ROC) curves were generated to determine biomarker potential. Results: A total of 236 erythrocyte miRNAs were identified. Of twelve differentially expressed miRNAs in RRMS two showed increased expression (adj. p < 0.05). Only modest fold-changes were evident across differentially expressed miRNAs. RT-qPCR confirmed differential expression of miR-30b-5p (0.61 fold, p < 0.05) and miR-3200-3p (0.36 fold, p < 0.01) in RRMS compared to healthy controls. Relative expression of miR-3200-5p (0.66 fold, NS p = 0.096) also approached significance. MiR-3200-5p was positively correlated with cognition measured by audio-recorded cognitive screen (r = 0.60; p < 0.01). MiR-3200-3p showed greatest biomarker potential as a single miRNA (accuracy = 75.5%, p < 0.01, sensitivity = 72.7%, specificity = 84.0%). Combining miR-3200-3p, miR-3200-5p, and miR-30b-5p into a composite biomarker increased accuracy to 83.0% (p < 0.05), sensitivity to 77.3%, and specificity to 88.0%. Conclusions: This is the first study to report differences in erythrocyte miRNAs in RRMS. While the role of miRNAs in erythrocytes remains to be elucidated, differential expression of erythrocyte miRNAs may be exploited as biomarkers and their potential contribution to MS pathology and cognition should be further investigated.
- Subject
- erythrocytes; microRNA; relapsing-remitting multiple sclerosis; next-generation sequencing
- Identifier
- http://hdl.handle.net/1959.13/1386519
- Identifier
- uon:32442
- Identifier
- ISSN:1755-8794
- Rights
- © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Language
- eng
- Full Text
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