MicroRNA-223 and miR-143 are important systemic biomarkers for disease activity in psoriasis
Introduction
Psoriasis is a chronic inflammatory disease of the skin [1]. Several attempts have been made to identify soluble biomarkers for psoriasis, however; there are still no specific biomarkers that can accurately predict disease progression and therapeutic response [2], [3], [4]. Hence, biomarkers for prognosis, response to treatment and even biomarkers related to comorbidities are needed to improve patient management and outcomes. MicroRNAs (miRNAs) are an abundant class of highly conserved small non-coding RNA molecules that modulate gene expression post-transcriptionally [5], [6], [7]. MicroRNAs act primarily within the cell, however; recent evidence has shown the presence of miRNAs in cell-free environments, including serum and plasma [8], [9] where they have proved stable and resistant to degradation of RNAses [10]. Thus, since the initial description of circulating miRNAs [8], [10], [11], [12] many efforts have been made to explore whether miRNAs can be used as diagnostic and prognostic tools for various diseases [13]. At present, the origin and biological significance of circulating miRNA still remain elusive; however, most circulating miRNAs may actually derive from blood cells [14], exosomes [15], apoptotic bodies [16], high-/low density lipoprotein [17] and/or RNA-binding proteins [18], [19]. Earlier studies on psoriasis-specific miRNA expression were primarily confined to skin tissue samples [20], [21], [22] and we have previously shown that changes in miRNA expression in the skin can be used as a diagnostic biomarker for skin diseases [23]. A few studies have investigated the miRNA expression in sera from patient with psoriasis [24], [25] and demonstrated that anti-TNFα therapy had a profound effect on the serum level of a number of miRNAs [26].
In this study we aimed to analyze the miRNA expression in different blood compartments from patients with psoriasis and healthy controls to explore miRNAs potential as blood biomarkers for psoriasis. We identified several deregulated miRNAs in the blood from patients with psoriasis among others miR-223 and miR-143 in the PBMCs from patients with psoriasis. Altogether our results suggest that changes in the miRNA expression in the blood from patients with psoriasis may become novel biomarkers for psoriasis.
Section snippets
Materials and methods
Detailed protocols are described in [50], [51].
MicroRNA expression in whole blood from patients with psoriasis
By collecting whole blood directly into a stabilizing agent that prevent further RNA transcription and degradation we sought to explore if the miRNA expression in whole blood can be used as a biomarker for psoriasis by capturing the miRNome at the time of blood collection. From 24 patients with mild to moderate psoriasis (PASI < 8) and 15 healthy controls we measured the global miRNA expression in whole blood. Clinical and demographic features are summarized in Table S2. In agreement with prior
Discussion
We undertook an explorative and comprehensive analysis of the miRNA expression in different blood compartments from patients with psoriasis and healthy controls aiming to explore the miRNAs potential to serve as blood biomarkers for psoriasis. We are, to our knowledge, the first to investigate the global miRNA expression in whole blood, plasma and PBMCs from patients with psoriasis. Our findings revealed significant changes in the miRNome of psoriatic blood, in particular miR-223 which
Statement of funding sources
This study was supported by the Ministry of Science, Innovation and Higher education, the Advanced Danish Technology Foundation and the Aage Bang Foundation.
Acknowledgements
We thank Nannie Bangsggard, Department of Dermato-Allergology, Gentofte Hospital for sample acquisition of the whole blood samples, Troels Marstrand, LEO Pharma A/S for valuable discussions during the manuscript preparation and the patients and healthy controls for their participation in the study.
References (51)
- et al.
MicroRNAs and other tiny endogenous RNAs in C. elegans
Curr Biol
(2003) MicroRNAs: genomics, biogenesis, mechanism, and function
Cell
(2004)MicroRNAs:target recognition and regulatory functions
Cell
(2009)- et al.
Circulating microRNAs: association with disease and potential use as biomarkers
Crit Rev Oncol Hematol
(2011) - et al.
MicroRNAs and potential target interactions in psoriasis
J Dermatol Sci
(2010) - et al.
Diagnostic microRNA profiling in cutaneous T-cell lymphoma (CTCL)
Blood
(2011) - et al.
Normalization of cDNA microarray data
Methods
(2003) - et al.
Cell membrane microparticles in blood and blood products: potentially pathogenic agents and diagnostic markers
Transfus Med Rev
(2006) - et al.
Platelet microRNA-mRNA coexpression profiles correlate with platelet reactivity
Blood
(2011) - et al.
MicroRNA function in myeloid biology
Blood
(2011)
Delayed processing of blood increases the frequency of activated CD11b+ CD15+ granulocytes which inhibit T cell function
J Immunol Methods
Platelet activation in patients with psoriasis: Increased plasma levels of platelet-derived microparticles and soluble P-selectin
J Am Acad Dermatol
Macrophage microvesicles induce macrophage differentiation and miR-223 transfer
Blood
Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCt method
Methods
Immunology of psoriasis
Annu Rev Immunol
Biomarkers in psoriasis and psoriatic arthritis
Ann Rheum Dis
A comprehensive review of biomarkers in psoriasis
Clin Exp Dermatol
Soluble biomarkers in psoriasis
Eur J Dermatol
Circulating microRNAs as stable blood-based markers for cancer detection
Proc Natl Acad Sci U S A
MicroRNAs in body fluids – the mix of hormones and biomarkers
Nat Rev Clin Oncol
Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases
Cell Res
Detection and characterization of placental microRNAs in maternal plasma
Clin Chem
Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma
Br J Haematol
Blood cell origin of circulating microRNAs: a cautionary note for cancer biomarker studies
Cancer Prev Res
Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells
Nat Cell Biol
Cited by (84)
Neutrophil-Derived MicroRNA-1290 Promotes Keratinocyte Proliferation in Psoriasis
2024, Journal of Investigative DermatologyMiR-15a-5p targets FOSL1 to inhibit proliferation and promote apoptosis of keratinocytes via MAPK/ERK pathway
2021, Journal of Tissue ViabilityMicroRNA-21 and MicroRNA-125b expression in skin tissue and serum as predictive biomarkers for psoriasis
2024, International Journal of DermatologyEvidence for the gut-skin axis: Common genetic structures in inflammatory bowel disease and psoriasis
2024, Skin Research and TechnologySerum miRNA profiling identified miRNAs associated with disease severity in psoriasis
2024, Experimental Dermatology