Multiple Sclerosis

Żurawska, Anna; Mycko, Marcin P.; Selmaj, Igor; Raine, Cedric S.; Selmaj, Krzysztof

doi:10.1212/nxi.0000000000001041

Cited by 21 publications

(18 citation statements)

References 50 publications

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“…They are critical regulators in the immune system, and are specifically expressed in specific organs, tissues, or cells. Accumulating evidence has highlighted the crucial potentials of circRNAs as diagnostic and therapeutic markers in multiple autoimmune diseases, including systemic lupus erythematosus (SLE), multiple sclerosis (MS), and RA [9][10][11]. Nevertheless, little is known of the effects and mechanism of circRNAs in regulating immune cell polarization and immune homeostatic imbalance.…”

Section: Introductionmentioning

confidence: 99%

circRNA_17725 Promotes Macrophage Polarization towards M2 by Targeting FAM46C to Alleviate Arthritis

Yang

et al. 2023

Mediators of Inflammation

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Accumulating studies have implicated that circular RNAs (circRNAs) play vital roles in the pathogenesis of rheumatoid arthritis (RA). Dysregulation of macrophage polarization leads to immune homeostatic imbalance in RA. However, the altering effects and mechanisms of circRNAs on macrophages polarization and immune homeostatic balance remain largely unclear. We aimed to investigate the potential role of circRNA_17725 in RA. The high-throughput sequence was performed to identify the dysregulated circRNAs in RA. We confirmed the data by CCK-8, EdU, and Annexin V/PI staining to elucidate the proliferation and apoptosis. The expressions of M1/M2-associated markers were confirmed using real-time PCR and flow cytometry analysis. Luciferase reporter assay and RNA Binding Protein Immunoprecipitation (RIP) were used to demonstrate the underlying mechanism of circRNA_17725. The altering effect of circRNA_17725 on macrophages in vivo was evaluated using collagen-induced arthritis (CIA) mouse model. circRNA_17725 was demonstrated to be downregulated in peripheral blood mononuclear cells and CD14+ monocytes from RA cases in contrast to healthy controls. The negative association between circRNA_17725 and the disease activity indexes (CRP, ESR, and DAS28) was observed, suggesting a vital role of circRNA_17725 in RA disease activity. Besides, after a coexpression analysis based on high-input sequencing and the bioinformatics analysis in MiRanda and TargetScan databases, a circRNA_17725-miR-4668-5p-FAM46C competing endogenous RNA (ceRNA) network was hypothesized. A series of cytology experiments in vitro have implicated that circRNA_17725 could inhibit the proliferation but enhance the apoptosis of macrophages. Decreased expression of TNF-α, IL-1β, and MMP-9 were observed in the supernatant of circRNA_17725-overexpressed Raw264.7 macrophages, implicating the inhibitory effect of circRNA_17725 on macrophage inflammatory mediators. Furthermore, circRNA_17725 could promote macrophage polarization towards M2 by targeting miR-4668-5p/FAM46C as a miRNA sponge. Additionally, circRNA_17725-overexpressed macrophages alleviated arthritis and protected against joint injuries and bone destruction by inducing macrophage polarization towards M2 in collagen-induced arthritis (CIA) mice. This study has suggested that circRNA_17725 regulated macrophage proliferation, apoptosis, inflammation, and polarization by sponging miR-4668-5p and upregulating FAM46C in RA.

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Section: Introductionmentioning

confidence: 99%

circRNA_17725 Promotes Macrophage Polarization towards M2 by Targeting FAM46C to Alleviate Arthritis

Yang

et al. 2023

Mediators of Inflammation

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“…Upon analyzing the expression results of AK2 and IKZP3, an upregulation of gene transcription was found (P = 5.65E-22, FC = 3.1; P = 1.72E-17, FC = 3.0, respectively). 84 CircRNAs as biomarkers for disability score in MS. Zurawska et al after found a circRNA biomarker that was associated with disability score. The group analyzed the downregulated circRNAs in the RRMS-relapse versus the RRMS-remission group versus HC.…”

Section: Differences In Circrna Expression Between Ms Patients and He...mentioning

confidence: 99%

Circular RNA in Multiple Sclerosis: Pathogenicity and Potential Biomarker Development: A Systematic Review

Mohammed

2023

Genet Epigenet

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Multiple sclerosis (MS) is a complex autoimmune disorder of the CNS that affects millions of people worldwide. The causes of the disease remain unknown despite extensive efforts to understand it. CircRNAs are a unique class of endogenous non-coding RNA that are abundant, stable, conserved, and specifically expressed molecules, making them a promising biomarker of diseases. This review investigates the role of circRNA in MS pathogenicity and their potential as a biomarker through a comprehensive literature search conducted in 8 scientific databases. The studies found that there are differentially expressed circRNAs in MS patients compared to healthy controls (HC), and this difference is even more pronounced in different MS subtypes. Enrichment of circRNAs in linkage disequilibrium (LD) blocks that harbor MS-associated SNPs suggests that these SNPs manipulate the levels of circRNAs in the surrounding area, contributing to disease pathogenicity. While circRNA shows promise as an indicator or biomarker for MS disease pathology, further research is needed to fully explore its potential and impact on human biology.

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“…In addition to circRNAs being implicated in the pathogenesis of MS, they have also been linked to disease activity. Accordingly, three (hsa_circRNA_101348, hsa_circRNA_102611, and hsa_circRNA_104361) circRNAs targeting 15 miRNAs and three additional protein-coding RNAs (of which 2 AK2 and IKZF3 are known to be involved in B-cell function) were measured to be overexpressed during a relapse [ 443 ]. The disease activity-related expression of various circRNAs was corroborated by a subsequent study, which has additionally described the sex-dependent increase of circRNA expression in MS, and furthermore has validated and proposed six additional circRNAs as potential biomarkers [ 431 ].…”

Section: Fluid Biomarkers Of Multiple Sclerosismentioning

confidence: 99%

Emerging Biomarkers of Multiple Sclerosis in the Blood and the CSF: A Focus on Neurofilaments and Therapeutic Considerations

Biernacki

Kokas

Sandi

et al. 2022

IJMS

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Introduction: Multiple Sclerosis (MS) is the most common immune-mediated chronic neurodegenerative disease of the central nervous system (CNS) affecting young people. This is due to the permanent disability, cognitive impairment, and the enormous detrimental impact MS can exert on a patient’s health-related quality of life. It is of great importance to recognise it in time and commence adequate treatment at an early stage. The currently used disease-modifying therapies (DMT) aim to reduce disease activity and thus halt disability development, which in current clinical practice are monitored by clinical and imaging parameters but not by biomarkers found in blood and/or the cerebrospinal fluid (CSF). Both clinical and radiological measures routinely used to monitor disease activity lack information on the fundamental pathophysiological features and mechanisms of MS. Furthermore, they lag behind the disease process itself. By the time a clinical relapse becomes evident or a new lesion appears on the MRI scan, potentially irreversible damage has already occurred in the CNS. In recent years, several biomarkers that previously have been linked to other neurological and immunological diseases have received increased attention in MS. Additionally, other novel, potential biomarkers with prognostic and diagnostic properties have been detected in the CSF and blood of MS patients. Areas covered: In this review, we summarise the most up-to-date knowledge and research conducted on the already known and most promising new biomarker candidates found in the CSF and blood of MS patients. Discussion: the current diagnostic criteria of MS relies on three pillars: MRI imaging, clinical events, and the presence of oligoclonal bands in the CSF (which was reinstated into the diagnostic criteria by the most recent revision). Even though the most recent McDonald criteria made the diagnosis of MS faster than the prior iteration, it is still not an infallible diagnostic toolset, especially at the very early stage of the clinically isolated syndrome. Together with the gold standard MRI and clinical measures, ancillary blood and CSF biomarkers may not just improve diagnostic accuracy and speed but very well may become agents to monitor therapeutic efficacy and make even more personalised treatment in MS a reality in the near future. The major disadvantage of these biomarkers in the past has been the need to obtain CSF to measure them. However, the recent advances in extremely sensitive immunoassays made their measurement possible from peripheral blood even when present only in minuscule concentrations. This should mark the beginning of a new biomarker research and utilisation era in MS.

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Multiple Sclerosis

Cited by 21 publications

References 50 publications

circRNA_17725 Promotes Macrophage Polarization towards M2 by Targeting FAM46C to Alleviate Arthritis

circRNA_17725 Promotes Macrophage Polarization towards M2 by Targeting FAM46C to Alleviate Arthritis

Circular RNA in Multiple Sclerosis: Pathogenicity and Potential Biomarker Development: A Systematic Review

Emerging Biomarkers of Multiple Sclerosis in the Blood and the CSF: A Focus on Neurofilaments and Therapeutic Considerations

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