Background Fibromyalgia (FM) is a clinical syndrome characterized by musculoskeletal pain and tenderness. Diagnosis is mainly based on exclusion of other resembling diseases since validated biological tests are still lacking. Identification of disease-related markers will enable clinicians to effectively diagnose FM, follow the progress of the disease, monitor the effects of therapeutic approaches and probably develop preventive programs.
MicroRNAs (miRNAs) are pieces of 18-25 nucleotides capable of regulating gene expression. Changes in their expression levels have been linked to environmental responses as well as to pathological processes. Their recent association to some other chronic diseases such as rheumatoid arthritis1, multiple sclerosis and chronic fatigue syndrome/myalgic encephalomyelitis2, made us think a signature miRNA profile might also be associated to fibromyalgia.
Objectives The objective of this study was to determine whether an association between an altered miRNAs expression profile and fibromyalgia exists.
Methods Total RNA extracted from Peripheral Blood Mononuclear Cells (PBMC) from 10 FM patients and 10 population matched healthy donors (mirVana™ miRNA Isolation Kit, Ambion, USA)(RIN>8) were subjected to miRNA profile analysis with 3D-Gene™ chips (Toray Industries, Japan) following manufacturer’s instructions. Quantitative RT-PCR amplification of miRNAs was performed in a LightCycler® 480 Real-TimePCR System (Roche, Switzerland) with the miScript SYBR GreenRT-PCR system (Qiagen, Germany) and the corresponding specific primer under standard amplification conditions. For comparison of the obtained signals, a Mann-Whitney U test was employed (p < 0.05).
Results A microarray screen including 10 FM patients and 10 population matched healthy donors showed that the levels of 4 miRNAs were consistently reduced by at least 4-fold in PBMCs of fibromyalgia patients as compared to matched healthy donor levels. A Mann-Whitney analysis of the results obtained by reverse transcription followed by quantitative PCR amplification of these 20 RNA samples confirmed that the expression levels of these 4 miRNAs are significantly lower (p <0.023) in all 10 FM patients while changes in other miRNAs tested resulted non-significant. This indicates that the 4 miRNAs identified have potential biomarker value. Targets of these miRNAs include positive regulators of erythroid anti-oxidant genes, membrane transporters and vascular contractility among other.
Conclusions The 4 miRNAs downregulated in the 10 FM patients analyzed represent potential diagnostic and prognostic biomarkers for the disease. Identification of their target genes in FM patients might help us understand the mechanisms behind this complex disease. However, further validation is required before the results can be transferred to a clinical setting.
Li J, Wan Y, Guo Q, Zou L, Zhang J, Fang Y, Zhang J, Zhang J, Fu X, Liu H, Lu L, Wu Y. Altered microRNA expression profile with miR-146a upregulation in CD4+ T cells from patients with rheumatoid arthritis. Arthritis Res Ther. 2010;12(3):R81.
Brenu EW, Ashton KJ, van Driel M, Staines DR, Peterson D, Atkinson GM, Marshall-Gradisnik SM. Cytotoxic lymphocyte microRNAs as prospective biomarkers for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. J Affect Disord. 2012 Dec 10;141(2-3):261-9.
Disclosure of Interest None Declared
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