Scavenging the hidden impacts of non-coding RNAs in multiple sclerosis

Multiple sclerosis (MS) is an early onset chronic neurological condition in adults characterized by inflammation, demyelination, gliosis, and axonal loss in the central nervous system. The pathological cause of MS is complex and includes both genetic and environmental factors. Non-protein-coding RNAs (ncRNAs), specifically miRNAs and lncRNAs, are important regulators of various biological processes. Over the past decade, many studies have investigated both miRNAs and lncRNAs in patients with MS. Since then, insightful knowledge has been gained in this field. Here, we review the role of miRNAs and lncRNAs in MS pathogenesis and discuss their implications for diagnosis and treatment.

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Expression analysis of long non-coding RNAs and their target genes in multiple sclerosis patients

Neurological Sciences ◽

10.1007/s10072-019-3720-3 ◽

2019 ◽

Vol 40 (4) ◽

pp. 801-811 ◽

Cited By ~ 3

Author(s):

Maziar Ganji ◽

Arezou Sayad ◽

Mir Davood Omrani ◽

Shahram Arsang-Jang ◽

Mehrdokht Mazdeh ◽

...

Keyword(s):

Multiple Sclerosis ◽

Expression Analysis ◽

Target Genes ◽

Non Coding Rnas ◽

Multiple Sclerosis Patients

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LncRNAs, MALAT1 and lnc-DC as potential biomarkers for multiple sclerosis diagnosis

Bioscience Reports ◽

10.1042/bsr20181335 ◽

2019 ◽

Vol 39 (1) ◽

Cited By ~ 8

Author(s):

Olfat G. Shaker ◽

Rania H. Mahmoud ◽

Omayma O. Abdelaleem ◽

Enas G. Ibrahem ◽

Abdelrahmaan A. Mohamed ◽

...

Keyword(s):

Multiple Sclerosis ◽

Tissue Specificity ◽

Positive Association ◽

Serum Levels ◽

Biological Functions ◽

Expression Levels ◽

Relapsing Remitting ◽

Non Coding Rnas ◽

Multiple Sclerosis Diagnosis ◽

Normal Controls

AbstractLong non-coding RNAs (lncRNAs) play an important role in gene regulation and show greater tissue specificity and complexity of biological functions. There is on-going research in their contribution in autoimmune diseases like multiple sclerosis (MS). Our study aimed at the evaluation of serum levels of lncRNAs, MALAT1 and lnc-DC in MS patients and the investigation of the association between these lncRNAs and the disease activity. Serum from 45 MS patients and 45 healthy controls was separated. MALAT1 and lnc-DC expression levels were assayed by qRT-PCR. MALAT1 and lnc-DC were significantly increased in MS patients (P=0.004 and P=0.006, respectively) in comparison with controls. There was a significant increase in expression of MALAT1 in secondary progressive MS (SPMS) subgroup compared with controls (P<0.0001); however, significant elevation of lnc-DC was demonstrated in relapsing remitting MS (RRMS) subtype (P=0.003) compared with normal controls. A positive association between the expression levels of MALAT1 and lnc-DC (r = 0.513, P < 0.0001) in MS patients was detected. Moreover, positive correlation was observed between MALAT1and lnc-DC in RRMS (r = 0.569, P = 0.001). Serum levels of MALAT1 and lnc-DC may serve as potential novel molecular biomarkers for MS diagnosis and may provide a new direction for its treatment.

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Prediction of probable impact of miR-34a and miR-215 on differentiation of naive CD4+ T cells to Th17 cells in multiple sclerosis

Journal of Shahrekord University of Medical Sciences ◽

10.34172/jsums.2019.48 ◽

2018 ◽

Vol 21 (6) ◽

pp. 276-279

Author(s):

Nooshin Ghadiri ◽

Aref Hoseini ◽

Kamran Ghaedi ◽

Negar Alsadat Emamnia ◽

Mazdak Ganjalikhani-Hakemi ◽

...

Keyword(s):

Multiple Sclerosis ◽

Th17 Cells ◽

Therapeutic Approaches ◽

Diagnostic Biomarkers ◽

Cellular Processes ◽

High Prevalence ◽

Probable Impact ◽

Non Coding Rnas ◽

Th17 Differentiation

Background and aims: miRNAs, as a class of non-coding RNAs, take part in different cellular processes. Dysregulation of different miRNAs has been reported in numerous disorders to date. Multiple sclerosis (MS) is an autoimmune disease with high prevalence in Iran and Th17 cells play an important role in its pathogenesis. In the current study, we aimed to predict the possible role of miR-34a and miR-215 in the process of controlling Th17 differentiation, and hence, their possible impact on the onset and progression of MS. Methods: We investigated probable interactions of miRNAs and genes that participate in Th17 cells differentiation using miRwalk database as an integrative one which utilizes 10 different algorithms to predict miRNA-mRNA interaction. Results: Based on our findings, miR-34a and miR-215 were predicted to have a potential role in the induction of Th17 cells differentiation. Conclusion: Conclusively, miR-34a and miR-215 may up-regulate Th17 cells of MS patients. Since bioinformatics data have shown that these miRNAs suppress negative regulatory genes in Th17 cells differentiation, we suppose that down-regulation of these miRNAs could ameliorate MS symptoms. Therefore, several therapeutic approaches may be considered for these miRNAs besides their application as valuable prognostic/diagnostic biomarkers in detection of various stages of MS.

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Insights into multiple sclerosis provided by non-coding RNAs: meeting summary from the symposium ‘Non-coding RNAs in autoimmune disorders of the central nervous system’ on 5 April 2013 in Warsaw, Poland

Multiple Sclerosis Journal ◽

10.1177/1352458514521518 ◽

2014 ◽

Vol 20 (11) ◽

pp. 1439-1442 ◽

Cited By ~ 1

Author(s):

Marcin P Mycko ◽

Howard L Weiner ◽

Krzysztof W Selmaj

Keyword(s):

Multiple Sclerosis ◽

Central Nervous System ◽

Cell Biology ◽

Potential Role ◽

Mechanisms Of Action ◽

Ribonucleic Acids ◽

The Central Nervous System ◽

Non Coding Rnas ◽

Autoimmune Demyelination

More than 80% of the human genome is biochemically active, whereas less than 3% of the genome encodes proteins. The emerging field of non-coding ribonucleic acids (RNAs) that are products of the genome, but do not program proteins, has revolutionized our understanding of cell biology. This was followed by a growing interest in the role of non-coding RNAs in the pathogenesis of human diseases, including multiple sclerosis (MS). In April 2013, a symposium in Warsaw, Poland, was the first meeting entirely dedicated to advances in the understanding of the roles of various subclasses of non-coding RNAs and showcased their involvement in autoimmune demyelination and MS. New mechanisms of action of small non-coding RNAs, as well as the advent of long non-coding RNAs were discussed, including the potential role of non-coding RNAs as MS biomarkers and their use for therapeutic intervention in MS.

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Small non-coding RNAs as important players, biomarkers and therapeutic targets in multiple sclerosis: A comprehensive overview

Journal of Autoimmunity ◽

10.1016/j.jaut.2019.04.002 ◽

2019 ◽

Vol 101 ◽

pp. 17-25 ◽

Cited By ~ 13

Author(s):

Eliane Piket ◽

Galina Yurevna Zheleznyakova ◽

Lara Kular ◽

Maja Jagodic

Keyword(s):

Multiple Sclerosis ◽

Therapeutic Targets ◽

Comprehensive Overview ◽

Non Coding Rnas

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Long Non-Coding RNAs, Novel Offenders or Guardians in Multiple Sclerosis: A Scoping Review

Frontiers in Immunology ◽

10.3389/fimmu.2021.774002 ◽

2021 ◽

Vol 12 ◽

Author(s):

Abbas Jalaiei ◽

Mohammad Reza Asadi ◽

Hani Sabaie ◽

Hossein Dehghani ◽

Jalal Gharesouran ◽

...

Keyword(s):

Multiple Sclerosis ◽

Neurodegenerative Diseases ◽

Demyelinating Disease ◽

Therapeutic Potential ◽

Regulation Of Gene Expression ◽

Diagnostic Significance ◽

Systematic Analysis ◽

Novel Treatments ◽

Non Coding Rnas

Multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the central nervous system, is one of the most common neurodegenerative diseases worldwide. MS results in serious neurological dysfunctions and disability. Disturbances in coding and non-coding genes are key components leading to neurodegeneration along with environmental factors. Long non-coding RNAs (lncRNAs) are long molecules in cells that take part in the regulation of gene expression. Several studies have confirmed the role of lncRNAs in neurodegenerative diseases such as MS. In the current study, we performed a systematic analysis of the role of lncRNAs in this disorder. In total, 53 studies were recognized as eligible for this systematic review. Of the listed lncRNAs, 52 lncRNAs were upregulated, 37 lncRNAs were downregulated, and 11 lncRNAs had no significant expression difference in MS patients compared with controls. We also summarized some of the mechanisms of lncRNA functions in MS. The emerging role of lncRNAs in neurodegenerative diseases suggests that their dysregulation could trigger neuronal death via still unexplored RNA-based regulatory mechanisms. Evaluation of their diagnostic significance and therapeutic potential could help in the design of novel treatments for MS.

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Contribution of hsa-miR-146a and hsa-miR-223 gene variations in patients with multiple sclerosis reveals association of rs2910164 and rs1044165 with risk of multiple sclerosis susceptibility

Journal of Investigative Medicine ◽

10.1136/jim-2020-001539 ◽

2021 ◽

pp. jim-2020-001539

Author(s):

Salar Shareef ◽

Seyed Omar Ebrahimi ◽

Somayeh Reiisi

Keyword(s):

Multiple Sclerosis ◽

Iranian Population ◽

Healthy Controls ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Mirna Genes ◽

Increased Risk ◽

Non Coding Rnas ◽

The Relationship ◽

Control Study

MicroRNAs (miRNAs) are a group of non-coding RNAs that play a role in gene regulation. Due to their possible functional importance, genetic variants within miRNA genes have been recognized as candidate biomarkers. Single-nucleotide polymorphisms (SNPs) in miRNA genes can be related to the risk of different autoimmune diseases. Some of these SNPs are rs2910164 in the miR-146a and rs1044165 in the miR-223. The aim of this study was to investigate the relationship between these polymorphisms and the risk of multiple sclerosis (MS) in an Iranian population. In this case–control study, 261 patients with MS and 250 healthy controls that matched by age and geographical region were enrolled. After sampling and genomic DNA extraction, genotyping was determined by PCR–restriction fragment length polymorphism. Allelic and genotypic associations between the SNPs and MS were evaluated by the data analysis conducted by SPSS V.20. The frequencies of rs2910164 and rs1044165 SNPs were significantly different between the patients with MS and healthy controls. C and T alleles in the variants rs2910164 and rs1044165, respectively, are associated with increased risk of MS. Such association was obtained in codominant, dominant, and overdominant models for both variants (OR ~3 and OR ~1.5, respectively). Furthermore, this study determined that the C and T alleles of rs2910164 and rs1044165 are risk factors for MS in the Iranian population.

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