MicroRNAs (miRNAs) are a class of short (~22 nucleotides) single-stranded RNAs that modulate the expression of multiple target mRNAs by inducing either translational repression or mRNA degradation. MiRNAs have emerged has key post-transcriptional regulators of diverse biological processes and their deregulation has been implicated in several complex human diseases, including neurodegenerative and inflammatory disorders. Multiple sclerosis (MS) is a multifactorial disease of the central nervous system characterized by chronic inflammation, demyelination, axonal damage, and progressive neurological dysfunction. In spite of extensive research, the molecular events involved in the initiation and progression of MS are still poorly understood. To be relevant for MS pathogenesis, candidate genes would be expected to be expressed either in tissues relevant for immune response, or in tissues affected by the disease process. Several miRNAs are known to be expressed specifically in the immune system and miRNA-dependent alterations in gene expression in hematopoietic cells are critical for mounting an appropriate immune response. Moreover, deregulation of hematopoietic-specific miRNA expression may result in defects in both central and peripheral tolerance. Therefore, we sought to explore the possible involvement of miRNAs in MS by monitoring for differential expression of specific miRNAs in peripheral blood mononuclear cells (PBMCs) of MS patients and healthy controls. We selected a set of 22 candidate miRNAs that are expressed in the immune system and/or are transcribed from previously reported MS susceptibility loci. The differential expression of candidate miRNAs in cases versus controls was evaluated using a microbead-based technology. In a pilot experiment, performed on PBMC RNA of relapsing-remitting MS patients and controls, 4 miRNAs resulted >3 folds up-regulated in MS vs controls, whereas only the miR-150 resulted down-regulated (2-fold decrease). Interestingly, two of the most up-regulated miRNAs, mir-155 and mir-146a, have been reported to be altered also in rheumatoid arthritis and systemic lupus erythematosus, suggesting shared pathogenic mechanisms between different chronic inflammatory diseases. This is, to our knowledge, the first evidence that the expression of specific miRNAs is altered in MS.

Differential expression of microRNAs in peripheral blood mononuclear cells of Multiple Sclerosis patients / G. Solda’, E.M. Paraboschi, D. Gemmati, P. Zamboni, S. Duga, R. Asselta. ((Intervento presentato al 59. convegno ASHG Annual Meeting tenutosi a Honolulu, HI nel 2009.

Differential expression of microRNAs in peripheral blood mononuclear cells of Multiple Sclerosis patients

G. Solda’
Primo
;
E.M. Paraboschi
Secondo
;
S. Duga
Penultimo
;
R. Asselta
Ultimo
2009

Abstract

MicroRNAs (miRNAs) are a class of short (~22 nucleotides) single-stranded RNAs that modulate the expression of multiple target mRNAs by inducing either translational repression or mRNA degradation. MiRNAs have emerged has key post-transcriptional regulators of diverse biological processes and their deregulation has been implicated in several complex human diseases, including neurodegenerative and inflammatory disorders. Multiple sclerosis (MS) is a multifactorial disease of the central nervous system characterized by chronic inflammation, demyelination, axonal damage, and progressive neurological dysfunction. In spite of extensive research, the molecular events involved in the initiation and progression of MS are still poorly understood. To be relevant for MS pathogenesis, candidate genes would be expected to be expressed either in tissues relevant for immune response, or in tissues affected by the disease process. Several miRNAs are known to be expressed specifically in the immune system and miRNA-dependent alterations in gene expression in hematopoietic cells are critical for mounting an appropriate immune response. Moreover, deregulation of hematopoietic-specific miRNA expression may result in defects in both central and peripheral tolerance. Therefore, we sought to explore the possible involvement of miRNAs in MS by monitoring for differential expression of specific miRNAs in peripheral blood mononuclear cells (PBMCs) of MS patients and healthy controls. We selected a set of 22 candidate miRNAs that are expressed in the immune system and/or are transcribed from previously reported MS susceptibility loci. The differential expression of candidate miRNAs in cases versus controls was evaluated using a microbead-based technology. In a pilot experiment, performed on PBMC RNA of relapsing-remitting MS patients and controls, 4 miRNAs resulted >3 folds up-regulated in MS vs controls, whereas only the miR-150 resulted down-regulated (2-fold decrease). Interestingly, two of the most up-regulated miRNAs, mir-155 and mir-146a, have been reported to be altered also in rheumatoid arthritis and systemic lupus erythematosus, suggesting shared pathogenic mechanisms between different chronic inflammatory diseases. This is, to our knowledge, the first evidence that the expression of specific miRNAs is altered in MS.
Settore BIO/11 - Biologia Molecolare
Settore BIO/13 - Biologia Applicata
American Society of Human Genetics
Differential expression of microRNAs in peripheral blood mononuclear cells of Multiple Sclerosis patients / G. Solda’, E.M. Paraboschi, D. Gemmati, P. Zamboni, S. Duga, R. Asselta. ((Intervento presentato al 59. convegno ASHG Annual Meeting tenutosi a Honolulu, HI nel 2009.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/69697
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