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Parkes, JE, Thoma, A, Lightfoot, AP, Day, PJ, Chinoy, H and Lamb, JA (2020) MicroRNA and mRNA profiling in the idiopathic inflammatory myopathies. BMC Rheumatology, 4 (1). ISSN 2520-1026
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MicroRNA and mRNA profiling in the idiopathic inflammatory myopathies.pdf - Published Version Available under License Creative Commons Attribution. Download (1MB) | Preview |
Abstract
Background: The idiopathic inflammatory myopathies (IIMs) are heterogeneous autoimmune conditions of skeletal muscle inflammation and weakness. MicroRNAs (miRNAs) are short, non-coding RNA which regulate gene expression of target mRNAs. The aim of this study was to profile miRNA and mRNA in IIM and identify miRNA-mRNA relationships which may be relevant to disease. Methods: mRNA and miRNA in whole blood samples from 7 polymyositis (PM), 7 dermatomyositis (DM), 5 inclusion body myositis and 5 non-myositis controls was profiled using next generation RNA sequencing. Gene ontology and pathway analyses were performed using GOseq and Ingenuity Pathway Analysis. Dysregulation of miRNAs and opposite dysregulation of predicted target mRNAs in IIM subgroups was validated using RTqPCR and investigated by transfecting human skeletal muscle cells with miRNA mimic. Results: Analysis of differentially expressed genes showed that interferon signalling, and anti-viral response pathways were upregulated in PM and DM compared to controls. An anti-Jo1 autoantibody positive subset of PM and DM (n = 5) had more significant upregulation and predicted activation of interferon signalling and highlighted T-helper (Th1 and Th2) cell pathways. In miRNA profiling miR-96-5p was significantly upregulated in PM, DM and the anti-Jo1 positive subset. RTqPCR replicated miR-96-5p upregulation and predicted mRNA target (ADK, CD28 and SLC4A10) downregulation. Transfection of a human skeletal muscle cell line with miR-96-5p mimic resulted in significant downregulation of ADK. Conclusion: MiRNA and mRNA profiling identified dysregulation of interferon signalling, anti-viral response and T-helper cell pathways, and indicates a possible role for miR-96-5p regulation of ADK in pathogenesis of IIM.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Dermatomyositis; Idiopathic inflammatory myopathies; Polymyositis; RNA sequencing; microRNA |
| Subjects: | Q Science > QH Natural history > QH301 Biology R Medicine > RM Therapeutics. Pharmacology |
| Divisions: | Pharmacy & Biomolecular Sciences |
| Publisher: | Springer |
| SWORD Depositor: | A Symplectic |
| Date Deposited: | 12 May 2022 11:46 |
| Last Modified: | 12 May 2022 12:00 |
| DOI or ID number: | 10.1186/s41927-020-00125-8 |
| URI: | https://researchonline.ljmu.ac.uk/id/eprint/16837 |
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