MicroRNA-29b variants and MxA expression change during interferon beta therapy in patients with relapsing-remitting multiple sclerosis (original) (raw)
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Iranian Journal of Allergy, Asthma and Immunology
T helper type 1 (Th1) and Th17 Cells with distinct cytokine profiles including interferon-gamma (IFN-γ) and interleukin 17 (IL-17) have a pivotal role in neuroinflammation and myelin destruction in the central nervous system (CNS) in MS. MicroRNA-29b (MiR-29b) and miR-326 contribute to regulating Th1 and Th17 differentiation and altered expression of the miRNAs could be associated with response to treatment in multiple sclerosis (MS). Therefore, our study aimed to evaluate the percentage of Th1 and Th17 and determining the expression levels of miR-29b-3p and miR-326 in these lymphocyte subpopulations between responsive and non-responsive to interferon beta (IFN-β) therapy in relapsing-remitting multiple sclerosis (RRMS) patients. The present study was performed on 40 RRMS patients following treatment with IFN-β. The percentage of Th1 cells and Th17 cells were determined by flow cytometry in responsive and nonresponsive patients. The expression levels of miR-29b-3p and miR-326 were a...
Volume 22, Number 1, Apr-Jun(Spring) 2020, Serial Number: 85, 2020
Objective: Multiple sclerosis (MS) is an inflammatory disease resulting in demyelination of the central nervous system (CNS). T helper 17 (Th17) subset protects the human body against pathogens and induces neuroinflammation, which leads to neurodegeneration. MicroRNAs (miRNAs) are a specific class of small (~22 nt) non-coding RNAs that act as post-transcriptional regulators. The expression of the miR-326 is highly associated with the pathogenesis of MS disease in patients through the promotion of Th17 development. Recently, studies showed that disease-modifying therapies (DMTs) could balance the dysregulation of miRNAs in the immune cells of patients with relapsing-remitting MS (RRMS). Interferon-beta (IFN-β) has emerged as one of the most common drugs for the treatment of RR-MS patients. The purpose of this study was to evaluate the expression of the miR-326 in RRMS patients who were responders and non-responders to IFN-β treatment. Materials and Methods: In this cross-sectional study, a total of 70 patients (35 responders and 35 non-responders) were enrolled. We analyzed the expression of the miR-326 in peripheral blood mononuclear cells (PBMCs) of RRMS patients at least one year after the initiation of IFN-β therapy. Real-time polymerase chain reaction (RT-PCR) was applied to measure the expression of the miR-326. Results: The results showed no substantial change in the expression of the miR-326 between responders and non-responders concerning the treatment with IFN-β. Although the expression of the miR-326 was slightly reduced in IFN-β-responders compared with IFN-β-non-responders; however, the reduction of the miR-326 was not statistically significant. Conclusion: Overall, since IFN-β doesn't normalize abnormal expression of miR-326, this might suggest that IFN-β affects Th17 development through epigenetic mechanisms other than miR-326 regulation. Citation: Fattahi M, Eskandari N, Sotoodehnejadnematalahi F, Shaygannejad V, Kazemi M. Comparison of the expression of miR-326 between interferon beta responders and non-responders in relapsing-remitting multiple sclerosis. Cell J. 2020; 22(1): 92-95.
International journal of molecular sciences, 2013
MicroRNAs (miRNAs) are small non-coding RNA molecules acting as post-transcriptional regulators of gene expression. They are involved in many biological processes, and their dysregulation is implicated in various diseases, including multiple sclerosis (MS). Interferon-beta (IFN-beta) is widely used as a first-line immunomodulatory treatment of MS patients. Here, we present the first longitudinal study on the miRNA expression changes in response to IFN-beta therapy. Peripheral blood mononuclear cells (PBMC) were obtained before treatment initiation as well as after two days, four days, and one month, from patients with clinically isolated syndrome (CIS) and patients with relapsing-remitting MS (RRMS). We measured the expression of 651 mature miRNAs and about 19,000 mRNAs in parallel using real-time PCR arrays and Affymetrix microarrays. We observed that the up-regulation of IFN-beta-responsive genes is accompanied by a down-regulation of several miRNAs, including members of the mir-2...
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.
Evaluation of serum miR-191-5p, miR-24-3p, miR-128-3p, and miR-376c-3 in multiple sclerosis patients
Acta Neurologica Scandinavica, 2018
Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS) where inflammatory and neurodegenerative events are the key characteristics, although progressive and relapsing subtypes show some differences in underlying immunological mechanisms. 1 Inflammation and focal disruption of the blood-brain barrier (BBB) lie behind the demyelination and neuronal loss in relapsing-remitting MS (RRMS), while in the progressive forms, neurodegeneration is mediated most likely without marked peripheral inflammation, and the role of CNS inflammation has been recognized also in PPMS. Disease-modifying treatments (DMT) decrease inflammation in active RRMS, 2 and this effect has now been observed in ocrelizumab-treated active RRMS and PPMS patients resulting in decrease in disability progression in both subtypes. 3,4 Blood-derived biomarkers that are able to detect disease activity in MS and segregate the disease subtypes may prove useful in personalized MS medicine, as blood collections are less invasive than collection of cerebrospinal fluid (CSF). Complexity in treatment decision making, due to heterogeneous pathology and clinical course of disease, creates the ultimate need for biomarkers that could enable early diagnosis and discriminate the aggressive disease course from
Decreased circulating miRNA levels in patients with primary progressive multiple sclerosis
Multiple Sclerosis Journal, 2013
Emerging evidence underlines the importance of micro(mi)RNAs in the pathogenesis of multiple sclerosis (MS). Freecirculating miRNAs were investigated in serum from MS patients compared to controls. Statistically significant decreased levels of miR-15b, miR-23a and miR-223 were observed in MS patients (p < 0.05). Results were validated and replicated in two further independent MS populations. A direct correlation between miRNA levels and the EDSS score was determined in PPMS (p < 0.007). The generalized trend toward miRNA down-regulation could result in over-expression of target genes involved in disease pathogenesis. Circulating miRNA profiling could thus represent a new avenue to identify easily detectable disease biomarkers.
Identification of MS-specific serum miRNAs in an international multicenter study
Neurology(R) neuroimmunology & neuroinflammation, 2018
To identify circulating microRNAs (miRNAs) linked to disease, disease stage, and disability in MS across cohorts. Samples were obtained from the Comprehensive Longitudinal Investigation of Multiple Sclerosis (CLIMB, Boston, MA), EPIC (San Francisco, CA), AMIR (Beirut, Lebanon) as part of the SUMMIT consortium, and Stockholm Prospective Assessment of Multiple Sclerosis (Stockholm, Sweden) cohorts. Serum miRNA expression was measured using locked nucleic acid-based quantitative PCR. Four groups were compared: (1) MS vs healthy control (HC), (2) relapsing-remitting (RR) vs HC, (3) secondary progressive (SP) vs HC, and (4) RR vs SP. A Wilcoxon rank-sum test was used for the comparisons. The association between each miRNA and the Expanded Disability Status Scale (EDSS) score was assessed using the Spearman correlation coefficient. For each comparison, the values were corrected for multiple comparisons using the approach of Benjamini and Hochberg to control the false discovery rate. In th...