Comprehensive analysis of microRNA profiles in multiple sclerosis including next-generation sequencing

Keller, Andreas; Leidinger, Petra; Steinmeyer, Florian; Stähler, Cord; Franke, André; Hemmrich-Stanisak, Georg; Kappel, Andreas; Wright, Ian; Dörr, Jan; Paul, Friedemann; Diem, Ricarda; Tocariu-Krick, Beatrice; Meder, Benjamin; Backes, Christina; Meese, Eckart; Ruprecht, Klemens

doi:10.1177/1352458513496343

Cited by 117 publications

(116 citation statements)

References 37 publications

(61 reference statements)

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“…17 Moreover, miR-16 overexpression promoted inhibition of FOXP3 in Tregs, thereby modifying them to a more conventional T-celllike function. 20 On the other hand, silencing of miR-16 pathway in conventional T cells may lead to an inducible Treg-like function by stimulating FOXP3 and CTLA-4 expression.…”

Section: Discussionmentioning

confidence: 99%

“…15 Abnormal miRNA function has been detected in several human diseases, including MS, 16 and is suggested as a disease biomarker and a potential therapeutic target. 15 In MS patients, aberrant expression of miR-16, 17 miR-155 18 and miR-142-3p 19 has been described. These miRNAs are involved in the regulation of T-cell activation, and their overexpression is related to T-cell-mediated autoimmune inflammation.…”

Section: Introductionmentioning

confidence: 99%

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Autologous hematopoietic SCT normalizes miR-16, -155 and -142-3p expression in multiple sclerosis patients

Arruda

Lorenzi

Sousa

et al. 2014

Bone Marrow Transplant

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Autologous hematopoietic SCT (AHSCT) has been investigated in the past as a therapeutic alternative for multiple sclerosis (MS). Despite advances in clinical management, knowledge about mechanisms involved with clinical remission post transplantation is still limited. Abnormal microRNA and gene expression patterns were described in MS and have been suggested as disease biomarkers and potential therapeutic targets. Here we assessed T-and B-cell reconstitution, microRNAs and immunoregulatory gene expression after AHSCT. Early immune reconstitution was mainly driven by peripheral homeostatic proliferation. AHSCT increased CD4 + CD25 hi FoxP3 + regulatory T-cell counts and expression of CTLA-4 and GITR (glucocorticoid-induced TNFR) on CD4 + CD25 hi T cells. We found transient increase in exhausted PD-1 + T cells and of suppressive CD8 + CD28 − CD57 + T cells. At baseline, CD4 + and CD8 + T cells from MS patients presented upregulated miR-16, miR-155 and miR-142-3p and downregulated FOXP3, FOXO1, PDCD1 and IRF2BP2. After transplantation, the expression of FOXP3, FOXO1, PDCD1 and IRF2BP2 increased, reaching control levels at 2 years. Expression of miR-16, miR-155 and miR-142-3p decreased towards normal levels at 6 months post therapy, remaining downregulated until the end of follow-up. These data strongly suggest that AHSCT normalizes microRNA and gene expression, thereby improving the immunoregulatory network. These mechanisms may be important for disease control in the early periods after AHSCT.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Autologous hematopoietic SCT normalizes miR-16, -155 and -142-3p expression in multiple sclerosis patients

Arruda

Lorenzi

Sousa

et al. 2014

Bone Marrow Transplant

View full text Add to dashboard Cite

show abstract

“…This also underlines the potential of miRNA biomarkers derived from peripheral blood for diagnostic purposes. Many groups investigated circulating miRNA profiles from serum for various diseases (non-ischemic systolic heart failure [13], pulmonary tuberculosis [14], non-small-cell lung cancer [15,16], breast cancer [17], prostate cancer [18], or ovarian cancer [19]), whereas we and others developed standardized operating procedures for measuring miRNA profiles from whole peripheral blood (myocardial infarction [20], lung cancer [21], multiple sclerosis [22,23], melanoma [24], ovarian cancer [25], chronic obstructive pulmonary disease [26], glioblastoma [27], and Alzheimer disease [28]). …”

Section: Introductionmentioning

confidence: 99%

miRNAs can be generally associated with human pathologies as exemplified for miR-144*

et al. 2014

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Background: miRNA profiles are promising biomarker candidates for a manifold of human pathologies, opening new avenues for diagnosis and prognosis. Beyond studies that describe miRNAs frequently as markers for specific traits, we asked whether a general pattern for miRNAs across many diseases exists. Methods: We evaluated genome-wide circulating profiles of 1,049 patients suffering from 19 different cancer and non-cancer diseases as well as unaffected controls. The results were validated on 319 individuals using qRT-PCR.

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“…[81,82]), as it provides the depth of sequence data to allow the exact quantification even of rare miRNA species. In this approach, purified miRNAs are first ligated to adaptors at both the 3′ and 5′ ends and subsequently converted into complementary DNA (cDNA).…”

Section: Ngsmentioning

confidence: 99%

miRNA assays in the clinical laboratory: workflow, detection technologies and automation aspects

Kappel

Keller

2017

Clinical Chemistry and Laboratory Medicine (CCLM)

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microRNAs (miRNAs) are short non-coding RNA molecules that regulate gene expression in eukaryotes. Their differential abundance is indicative or even causative for a variety of pathological processes including cancer or cardiovascular disorders. Due to their important biological function, miRNAs represent a promising class of novel biomarkers that may be used to diagnose life-threatening diseases, and to monitor disease progression. Further, they may guide treatment selection or dosage of drugs. miRNAs from blood or derived fractions are particularly interesting candidates for routine laboratory applications, as they can be measured in most clinical laboratories already today. This assures a good accessibility of respective tests. Albeit their great potential, miRNA-based diagnostic tests have not made their way yet into the clinical routine, and hence no standardized workflows have been established to measure miRNAs for patients' benefit. In this review we summarize the detection technologies and workflow options that exist to measure miRNAs, and we describe the advantages and disadvantages of each of these options. Moreover, we also provide a perspective on data analysis aspects that are vital for translation of raw data into actionable diagnostic test results.

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Comprehensive analysis of microRNA profiles in multiple sclerosis including next-generation sequencing

Cited by 117 publications

References 37 publications

Autologous hematopoietic SCT normalizes miR-16, -155 and -142-3p expression in multiple sclerosis patients

Autologous hematopoietic SCT normalizes miR-16, -155 and -142-3p expression in multiple sclerosis patients

miRNAs can be generally associated with human pathologies as exemplified for miR-144*

miRNA assays in the clinical laboratory: workflow, detection technologies and automation aspects

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