Expression Profile of Selected MicroRNAs in the Peripheral Blood of Multiple Sclerosis Patients: a Multivariate Statistical Analysis with ROC Curve to Find New Biomarkers for Fingolimod

Eftekharian, Mohammad Mahdi; Komaki‬, Alireza; Mazdeh, Mehrdokht; Arsang‐Jang, Shahram; Taheri, Mohammad; Ghafouri‐Fard, Soudeh

doi:10.1007/s12031-019-01294-z

Cited by 20 publications

(20 citation statements)

References 26 publications

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“…It has also been shown that low expression of miR-524-5p in thyroid papillary carcinoma increases the expression levels of Forkhead box protein E1 and integrin subunit α3 in thyroid papillary carcinoma, thus inhibiting cell migration and proliferation and promoting apoptosis (27). Eftekharian et al (30) demonstrated that the expression of miR-524-5p was significantly lower in the peripheral blood of patients with multiple sclerosis compared with healthy controls. Moreover, miR-524-5p can be used as a biomarker of the response to fengomod in patients with multiple sclerosis (30).…”

Section: Discussionmentioning

confidence: 99%

“…Eftekharian et al (30) demonstrated that the expression of miR-524-5p was significantly lower in the peripheral blood of patients with multiple sclerosis compared with healthy controls. Moreover, miR-524-5p can be used as a biomarker of the response to fengomod in patients with multiple sclerosis (30). Zhao et al (31) also revealed that high expression levels of miR-524-3p and miR-524-5p inhibit the TGF-β, Notch and Hippo pathways by targeting SMAD2, hairy and enhancer of split-1 and TEA domain transcription factor 1, respectively.…”

Section: Discussionmentioning

confidence: 99%

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Detection of microRNA expression levels based on microarray analysis for classification of idiopathic pulmonary fibrosis

Zheng

et al. 2020

Exp Ther Med

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The etiology and pathophysiological mechanisms of idiopathic pulmonary fibrosis (IPF) are yet to be fully elucidated; however, mining of disease-related microRNAs (miRNAs/miRs) has improved the understanding of the progression of IPF. The aim of the current study was to screen miRNAs associated with IPF using three mathematical algorithms: One-way ANOVA, least absolute shrinkage and selector operation (LASSO) and support vector machinerecursive feature elimination (SVM-RFE). Using ANOVA, three miRNAs and two miRNAs were selected with opposite expression patterns in moderate and severe IPF, respectively. In total, two algorithms, LASSO and SVM-RFE, were used to perform feature selection of miRNAs. miRNAs from patients were also extracted from formalin-fixed paraffin-embedded tissues and detected using reverse transcription-quantitative PCR (RT-qPCR). The intersection of the three algorithms (ANOVA, LASSO and SVM-RFE) was taken as the final result of the miRNA candidates. Three miRNA candidates, including miR-124, hsa-miR-524-5p and hsa-miR-194 were therefore used as biomarkers. The receiver operating characteristic model demonstrated favorable discrimination between IPF and control groups, with an area under the curve of 78.5%. Moreover, RT-qPCR results indicated that miR-124, hsa-miR-524-5p, hsa-miR-194 and hsa-miR-133a were differentially expressed between patients with IPF and age-matched men without fibrotic lung disease. The target genes of these miRNAs were further predicted and Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed. Collectively, the present results suggested that the identified miRNAs associated with IPF may be useful biomarkers for the diagnosis of this disease.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Detection of microRNA expression levels based on microarray analysis for classification of idiopathic pulmonary fibrosis

Zheng

et al. 2020

Exp Ther Med

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“…These results are important as they indicate that targeting Cer biosynthetic pathways for alteration in levels of specific miRNAs may provide significant therapeutic benefits in relapsing remitting MS patients. A detailed overview of the experimental design and findings of studies investigating miRNAs as potential biomarkers of MS have recently been published [78], which may help in designing efficient miRNAs in future MS therapy. An approach of MS therapy can be initiated by targeting SPT regulation by selecting one or more from a group of miRNAs such as miR-376, miR-30, miR-128, miR-126, miR-7, and miR-9, as these miRNAs are involved in interfering with Cer synthesis [49].…”

Section: Msmentioning

confidence: 99%

Ceramide and Sphingosine Regulation of Myelinogenesis: Targeting Serine Palmitoyltransferase Using microRNA in Multiple Sclerosis

Dasgupta

Ray

2019

IJMS

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Ceramide and sphingosine display a unique profile during brain development, indicating their critical role in myelinogenesis. Employing advanced technology such as gas chromatography–mass spectrometry, high performance liquid chromatography, and immunocytochemistry, along with cell culture and molecular biology, we have found an accumulation of sphingosine in brain tissues of patients with multiple sclerosis (MS) and in the spinal cord of rats induced with experimental autoimmune encephalomyelitis. The elevated sphingosine leads to oligodendrocyte death and fosters demyelination. Ceramide elevation by serine palmitoyltransferse (SPT) activation was the primary source of the sphingosine elevation as myriocin, an inhibitor of SPT, prevented sphingosine elevation and protected oligodendrocytes. Supporting this view, fingolimod, a drug used for MS therapy, reduced ceramide generation, thus offering partial protection to oligodendrocytes. Sphingolipid synthesis and degradation in normal development is regulated by a series of microRNAs (miRNAs), and hence, accumulation of sphingosine in MS may be prevented by employing miRNA technology. This review will discuss the current knowledge of ceramide and sphingosine metabolism (synthesis and breakdown), and how their biosynthesis can be regulated by miRNA, which can be used as a therapeutic approach for MS.

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“…Treatment of non-responder patients is a critical issue in the clinical management of MS and, unfortunately, it remains a widely unexplored field [18]. Eftekharian et al [93] investigated for the first time the miRNA involvement in MS drug resistance and showed different miRNA patterns in MS patients responding to Fingolimod compared to non-responders. In their preliminary study, miR-34a-5p and miR-211-5p were found down-regulated in non-responder patients compared to responders, while miR-204-5p was up-regulated [93].…”

Section: Mirnas Involved In Ms Drug Resistancementioning

confidence: 99%

“…Eftekharian et al [93] investigated for the first time the miRNA involvement in MS drug resistance and showed different miRNA patterns in MS patients responding to Fingolimod compared to non-responders. In their preliminary study, miR-34a-5p and miR-211-5p were found down-regulated in non-responder patients compared to responders, while miR-204-5p was up-regulated [93]. Serum exosomal miRNAs were found to be altered after treatment with Fingolimod [94].…”

Section: Mirnas Involved In Ms Drug Resistancementioning

confidence: 99%

Precision Medicine in Neurodegenerative Diseases: Some Promising Tips Coming from the microRNAs’ World

Nuzziello

Ciaccia

Liguori

2019

Cells

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Novel insights in the development of a precision medicine approach for treating the neurodegenerative diseases (NDDs) are provided by emerging advances in the field of pharmacoepigenomics. In this context, microRNAs (miRNAs) have been extensively studied because of their implication in several disorders related to the central nervous system, as well as for their potential role as biomarkers of diagnosis, prognosis, and response to treatment. Recent studies in the field of neurodegeneration reported evidence that drug response and efficacy can be modulated by miRNA-mediated mechanisms. In fact, miRNAs seem to regulate the expression of pharmacology target genes, while approved (conventional and non-conventional) therapies can restore altered miRNAs observed in NDDs. The knowledge of miRNA pharmacoepigenomics may offers new clues to develop more effective treatments by providing novel insights into interindividual variability in drug disposition and response. Recently, the therapeutic potential of miRNAs is gaining increasing attention, and miRNA-based drugs (for cancer) have been under observation in clinical trials. However, the effective use of miRNAs as therapeutic target still needs to be investigated. Here, we report a brief review of representative studies in which miRNAs related to therapeutic effects have been investigated in NDDs, providing exciting potential prospects of miRNAs in pharmacoepigenomics and translational medicine.

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Expression Profile of Selected MicroRNAs in the Peripheral Blood of Multiple Sclerosis Patients: a Multivariate Statistical Analysis with ROC Curve to Find New Biomarkers for Fingolimod

Cited by 20 publications

References 26 publications

Detection of microRNA expression levels based on microarray analysis for classification of idiopathic pulmonary fibrosis

Detection of microRNA expression levels based on microarray analysis for classification of idiopathic pulmonary fibrosis

Ceramide and Sphingosine Regulation of Myelinogenesis: Targeting Serine Palmitoyltransferase Using microRNA in Multiple Sclerosis

Precision Medicine in Neurodegenerative Diseases: Some Promising Tips Coming from the microRNAs’ World

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