Selected Extracellular microRNA as Potential Biomarkers of Multiple Sclerosis Activity—Preliminary Study (original) (raw)
Related papers
MicroRNAs as Diagnostic and Therapeutic Targets in Multiple Sclerosis
Multiple sclerosis (MS) is a chronic devastating disease of the central nervous system (CNS), which is reported to be the most common neuroinflammatory disorder of the young adults. Although the underlying etiology of MS is not completely elucidated, the number of patients and burden to societies increases worldwide. There are several CNS disorders that might have overlapping phenotypic manifestations with MS; therefore, reliable and accessible diagnostic test is highly desirable for differential diagnosis. MicroRNAs (miRNAs) are small regulatory RNAs that are proven to be master regulators of gene expression. Recently, several studies have shown potential roles for miRNAs in development, hemostasis and maturation of immune system, suggesting possible involvement of these regulatory elements in autoimmune diseases, such as MS. We reviewed recent literature to explore miRNAs that are reported to be involved in pathogenesis of MS and found some miRNAs that might have potentials as being diagnostic biomarkers.
MicroRNAs in gray and white matter multiple sclerosis lesions: impact on pathophysiology
The Journal of Pathology, 2020
Multiple sclerosis (MS) is a chronic disease of the CNS, hallmarked by inflammation and demyelination. Early stages of the disease frequently show active lesions containing numerous foamy macrophages and inflammatory cells. Disease progression is highlighted by increasing numbers of mixed active/inactive or inactive lesions showing sparse inflammation and pronounced astrogliosis. Furthermore, gray matter lesions increase in number and extent during disease progression. MicroRNAs (miRNAs) comprise a group of several thousand (in humans more than 2000), small non-coding RNA molecules with a fundamental influence on about one-third of all protein-coding genes. Furthermore, miRNAs have been detected in body fluids, including spinal fluid, and they are assumed to participate in intercellular communications. Several studies have determined miRNA profiles from dissected white and gray matter lesions of autoptic MS patients. In this review, we summarize in detail the current knowledge of individual miRNAs in gray and white matter lesions of MS patients and present the concepts of MS tissue lesion development based on the altered miRNA profiles.
Expression, regulation and function of microRNAs in multiple sclerosis
International journal of medical sciences, 2014
MicroRNAs (miRNAs) are single-stranded 19-25 nucleotide-long RNAs and have an important role in post-transcriptional gene silencing. It has been demonstrated that miRNAs are dysregulated in patients with multiple sclerosis (MS). For instance, miR-21, miR-142-3p, miR-146a, miR-146b, miR-155 and miR-326 were up-regulated in both peripheral blood mononuclear cells (PBMCs) and brain white matter lesions from MS patients and mouse model as well. These up-regulated miRNAs may be used as a signature for MS and play critical roles in MS pathogenesis. Moreover, miR-15a, miR-19a, miR-22, miR-210 and miR-223 were up-regulated in both regulatory T cells (Tregs) and other samples such as plasma, blood cells, PBMCs and brain white matter tissues from MS patients, suggesting that these up-regulated miRNAs and Tregs may also play a role in MS pathogenesis. Contrarily, other miRNAs such as miR-15a, miR-15b, miR-181c and miR-328 were down-regulated in MS. Drugs such as interferon-β and glatiramer acetate for MS treatment may regulate miRNA expression and thus have benefits for MS patients. The dysregulated miRNAs such as miR-155 and miR-326 may be used as diagnostic markers and therapeutic targets for MS.
Neuroscience Letters, 2012
Identification of novel targets and biomarkers, such as microRNAs, is extremely helpful to understand the pathogenetic mechanisms in a disease like multiple sclerosis (MS). We tested the expression profile of 1145 microRNAs in peripheral blood mononuclear cells (PBMCs) of 19 MS patients and 14 controls, and we further explored their function by performing a whole-genome mRNA profiling in same subjects and using bioinformatic prediction tool. A total of 104 miRNAs have been identified as deregulated in MS patients; 2/10 which ranked highest (let-7g and miR-150) have been validated in a replication sample, leading to the identification of putative target genes.
Differentially expressed microRNA in multiple sclerosis: A window into pathogenesis?
Clinical and Experimental Neuroimmunology, 2014
MicroRNA are small non-coding RNA that mediate mRNA translation repression or mRNA degradation, and thereby refine protein expression levels. More than 30-60% of all genes are regulated by microRNA. Exploring disease-related microRNA signatures is an emerging tool in biomarker discovery, and silencing has already been used in a clinical phase 2a trial. As microRNA regulate translation of more than 100 genes, they could also provide a focused insight into important pathways, and offer a better understanding of diseases with heterogeneous pathogenesis. The number of studies investigating microRNA related to multiple sclerosis has increased significantly in recent years. Differentially expressed microRNA have been identified in the whole blood, serum, plasma, cerebrospinal fluid, peripheral blood mononuclear cells, blood-derived cell subsets and brain lesions of patients with multiple sclerosis. Most studies applied a non-candidate approach of screening by microarray and validation by quantitative polymerase chain reaction or next generation sequencing; others used a candidate-driven approach. Despite a relatively high number of multiple sclerosisassociated microRNA, just a few could be repeatedly found, even if similar biological materials were examined. Only part of the identified microRNA has been extensively studied, and the biological function has not been explored in the majority. Some of the microRNA related to multiple sclerosis are also differentially expressed in other autoimmune diseases or autoimmune models. In the present review, we discuss microRNA related to disease compartments, activity and phenotype. We also focus on several microRNA with well-defined functions, or because of particular interest due to either validation by several independent studies or in-depth exploration of function. (Clin. Exp. Neuroimmunol.
Pathophysiology of translational regulation by microRNAs in multiple sclerosis
FEBS Letters, 2011
MicroRNAs (miRNAs) comprise a group of several hundred, small non-coding RNA molecules with a fundamental influence on the regulation of gene expression. Certain miRNAs are altered in blood cells of multiple sclerosis (MS), and active and inactive MS brain lesions have distinct miRNA expression profiles. Several miRNAs such as miR-155 or miR-326 are considerably overexpressed in active MS lesions versus controls, and mice lacking these miRNAs either through knockout (miR-155) or by in vivo silencing (miR-326) show a reduction of symptoms in experimental autoimmune encephalomyelitis (EAE), a model system for multiple sclerosis. This review describes miRNAs regulated in the blood or in brain lesions of MS patients in the context of their previously described functions in physiology and pathophysiology.
MicroRNAs and Multiple Sclerosis
Autoimmune Diseases, 2011
MicroRNAs (miRNAs) have recently emerged as a new class of modulators of gene expression. miRNAs control protein synthesis by targeting mRNAs for translational repression or degradation at the posttranscriptional level. These noncoding RNAs are endogenous, single-stranded molecules approximately 22 nucleotides in length and have roles in multiple facets of immunity, from regulation of development of key cellular players to activation and function in immune responses. Recent studies have shown that dysregulation of miRNAs involved in immune responses leads to autoimmunity. Multiple sclerosis (MS) serves as an example of a chronic and organ-specific autoimmune disease in which miRNAs modulate immune responses in the peripheral immune compartment and the neuroinflammatory process in the brain. For MS, miRNAs have the potential to serve as modifying drugs. In this review, we summarize current knowledge of miRNA biogenesis and mode of action and the diverse roles of miRNAs in modulating the immune and inflammatory responses. We also review the role of miRNAs in autoimmunity, focusing on emerging data regarding miRNA expression patterns in MS. Finally, we discuss the potential of miRNAs as a disease marker and a novel therapeutic target in MS. Better understanding of the role of miRNAs in MS will improve our knowledge of the pathogenesis of this disease.
Expression and Genetic Analysis of MicroRNAs Involved in Multiple Sclerosis
International Journal of Molecular Sciences, 2013
Evidence underlines the importance of microRNAs (miRNAs) in the pathogenesis of multiple sclerosis (MS). Based on the fact that miRNAs are present in human biological fluids, we previously showed that miR-223, miR-23a and miR-15b levels were downregulated in the sera of MS patients versus controls. Here, the expression levels of these candidate miRNAs were determined in peripheral blood mononuclear cells (PBMCs) and the serum of MS patients, in addition to three genotyped single nucleotide polymorphisms (SNPs). Mapping in the genomic regions of miR-223, miR-23a and miR-15b genes, 399 cases and 420 controls were tested. Expression levels of miR-223 and miR-23a were altered in PBMCs from MS patients versus controls. Conversely, there were no differences in the expression levels of miR-15b. A significantly decreased genotypic frequency of miR-223 rs1044165 T/T genotype was observed in MS patients. Moreover, the allelic frequency of miR-23a rs3745453 C allele was significantly increased in patients versus controls. In contrast, there were no differences in the distribution of miR-15b SNP.
Circulating MicroRNAs as biomarkers for disease staging in multiple sclerosis
Annals of Neurology, 2013
Objective: MicroRNA (miRNAs) are single stranded, small non-coding RNAs that regulate gene expression. Because they are stable in serum, they are being developed as biomarkers for cancer and other diseases. In MS, miRNAs have been studied in cell populations but not in the circulation. In MS a major challenge is to develop immune biomarkers to monitor disease. We asked if circulating miRNAs could be identified in MS and whether they linked to disease stage and/or disability. Methods: 368 miRNAs were measured in EDTA plasma in 10 RRMS, 9 SPMS and 9 healthy controls (HC) using qPCR and Exiqon Human Panel I assays. 19 miRNAs from this discovery set were validated using qPCR on an independent set of 50 RRMS, 51 SPMS and 32 HCs. Results: We found that circulating miRNAs are differentially expressed in RRMS and SPMS vs. HC and in RRMS vs. SPMS. We also found miRNAs linked to EDSS. hsa-miR-92a-1* was identified in the largest number of comparisons. It was different in RRMS vs. SPMS, RRMS vs. HC and showed association with EDSS and disease duration. miR-92 has target genes involved in cell cycle regulation and cell signaling. The let-7 family of miRNAs differentiated SPMS vs. HC and RRMS vs. SPMS. Let-7 miRNAs regulate stem cell differentiation, T cell activation, activate TLR-7 and are linked to neurodegeneration. hsa-miR-454 differentiated RRMS vs. SPMS and hsa-miR-145 differentiated RRMS vs. HC and RRMS vs. SPMS; both were associated with EDSS. Interestingly, the same circulating miRNAs (let-7 and miR-92) that were differentially expressed in RRMS vs. SPMS