Elevated Serum MicroRNA Let-7c in Moyamoya Disease

Zhao, Shaoyun; Gong, Zhe; Zhang, Jing; Xu, Xiaoge; Liu, Peidong; Guan, Wenjuan; Jing, Lijun; Peng, Tao; Teng, Jie; Jia, Yanjie

doi:10.1016/j.jstrokecerebrovasdis.2015.01.041

Cited by 12 publications

(14 citation statements)

References 49 publications

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“…Therefore, other genetic variants, including RNF213 rare variants, environmental factors, or epigenetic mechanisms may also be involved in the disease pathogenesis. 6,8–10) Circulating microRNAs (miRNAs) in blood have been reported to be differentially expressed in MMD patients and thus, are considered as potential factors involved in disease progression or modifications. 8,10) To facilitate such analyses, blood samples could be collected at several time points pertaining to the clinical events of patients.…”

Section: Discussionmentioning

confidence: 99%

“…6,8–10) Circulating microRNAs (miRNAs) in blood have been reported to be differentially expressed in MMD patients and thus, are considered as potential factors involved in disease progression or modifications. 8,10) To facilitate such analyses, blood samples could be collected at several time points pertaining to the clinical events of patients. Therefore, combined with longitudinal clinical data in the registry, analysis of the epigenetic changes could be performed, which potentially could be used for prediction of disease progression.…”

Section: Discussionmentioning

confidence: 99%

“…4–7) Other studies have suggested that mechanisms involving epigenetic/environmental factors may also be associated with disease progression. 6,8–10) The Biobank system will effectively collect a large number of samples nationwide. In combination with blood samples, the longitudinal clinical data stratified according to demographics or neuroimaging data may elucidate novel genetic/epigenetic markers associated with the onset of disease, various clinical subtypes, and disease progression.…”

Section: Introductionmentioning

confidence: 99%

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Proposal for a Prospective Registry for Moyamoya Disease in Japan

Kazumata

Ito

Uchino

et al. 2017

Neurol. Med. Chir.(Tokyo)

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The number of clinical research papers published worldwide on moyamoya disease (MMD) has increased recently. However, the majority of the literature comprises retrospective single-center studies collecting data on small numbers of patients. Several multi-center studies are ongoing in Japan; however, the current data are insufficient for comprehensively outlining the various characteristics of MMD. To enhance our knowledge on epidemiologic, vascular, and genetic aspects of MMD, a prospective multicenter registry will be established in Japan that will help to streamline clinical research as well as improve clinical treatments and long-term outcomes. Patients with MMD or secondary moyamoya syndrome referred to the participating centers will be invited to the registry. Demographic and physiological parameters, along with neuroimaging data will be collected chronologically. Clinical events, including neurological, medical, and surgical interventions will be recorded. Whole blood samples will be collected. Extra- and intracranial vascular tissue, and/or cerebrospinal fluid will also be collected from patients who undergo surgical revascularization. These biospecimens will be stored at the repositories and utilized for genome-wide association studies for identifying genetic variants, as well as tissue-specific proteomic, and/or molecular analyses. Ethics approval will be obtained at all facilities collecting biospecimens. The registry will provide descriptive statistics on functional outcomes, surgical techniques used, medications, and neurological events stratified according to patients’ clinical characteristics. We expect this study to provide novel insights in the management of MMD patients and design better therapies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Proposal for a Prospective Registry for Moyamoya Disease in Japan

Kazumata

Ito

Uchino

et al. 2017

Neurol. Med. Chir.(Tokyo)

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“…A study reported significantly elevated plasma concentrations of matrix metalloproteinase 9 (MMP-9), monocyte chemoattractant protein-1, interleukin-1β, vascular endothelial growth factor (VEGF), and platelet-derived growth factor subunit B but lower plasma concentrations of MMP-3 and tissue inhibitors of metalloproteinase (TIMP)-1 and -2 in patients with MMD compared with the healthy controls [ 3 ]. Furthermore, serum microRNA let-7c, alpha-1-antitrypsin, and MMP-9 may serve as potential biomarkers for MMD diagnosis [ 4 - 6 ]. CSF cellular retinoic acid-binding protein-I, basic fibroblast growth factor (FGF), soluble vascular cell adhesion molecule 1, intercellular adhesion molecule 1, and E-selectin levels may also serve as MMD biomarkers [ 7 - 9 ].…”

Section: Introductionmentioning

confidence: 99%

Aberrant Promoter Hypomethylation of Sortilin 1: A Moyamoya Disease Biomarker

et al. 2018

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Background and PurposeThe pathogenesis of moyamoya disease (MMD) remains poorly understood, and no reliable molecular biomarkers for MMD have been identified to date. The present study aimed to identify epigenetic biomarkers for use in the diagnosis of MMD. MethodsWe performed integrated analyses of gene expression profiles and DNA methylation profiles in endothelial colony forming cells (ECFCs) from three patients with MMD and two healthy individuals. Candidate gene mRNA expression and DNA methylation status were further validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and pyrosequencing analysis of an expanded ECFC sample set from nine patients with MMD and ten controls. We evaluated the diagnostic accuracy of the potential biomarkers identified here using receiver operating characteristic curve analyses and further measured major angiogenic factor expression levels using a tube formation assay and RT-qPCR. ResultsFive candidate genes were selected via integrated analysis; all five were upregulated by hypomethylation of specific promoter CpG sites. After further validation in an expanded sample set, we identified a candidate biomarker gene, sortilin 1 (SORT1). DNA methylation status at a specific SORT1 promoter CpG site in ECFCs readily distinguished patients with MMD from the normal controls with high accuracy (area under the curve 0.98, sensitivity 83.33%, specificity 100%). Furthermore, SORT1 overexpression suppressed endothelial cell tube formation and modulated major angiogenic factor and matrix metalloproteinase-9 expression, implying SORT1 involvement in MMD pathogenesis. ConclusionsOur findings suggest that DNA methylation status at the SORT1 promoter CpG site may be a potential biomarker for MMD.

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“…We, therefore, conducted circulating genome-wide microRNA (miRNome) profiling in cohorts of MMD-discordant monozygotic twins, non-twin MMD cases, and healthy controls to unmask potential confounders from a previously reported microRNA signature in MMD [ 16 , 17 ]. We further studied endothelial microRNA expression using iPS cell lines of another independent non-twin cohort as an in vitro MMD model.…”

Section: Introductionmentioning

confidence: 99%

Circulating miRNome profiling in Moyamoya disease-discordant monozygotic twins and endothelial microRNA expression analysis using iPS cell line

et al. 2018

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BackgroundMoyamoya disease (MMD) is characterized by progressive stenosis of intracranial arteries in the circle of Willis with unknown etiology even after the identification of a Moyamoya susceptible gene, RNF213. Recently, differences in epigenetic regulations have been investigated by a case-control study in MMD. Here, we employed a disease discordant monozygotic twin-based study design to unmask potential confounders.MethodsCirculating genome-wide microRNA (miRNome) profiling was performed in MMD-discordant monozygotic twins, non-twin-MMD patients, and non-MMD healthy volunteers by microarray followed by qPCRvalidation, using blood samples. Differential plasma-microRNAs were further quantified in endothelial cells differentiated from iPS cell lines (iPSECs) derived from another independent non-twin cohort. Lastly, their target gene expression in the iPSECs was analyzed.ResultsMicroarray detected 309 plasma-microRNAs in MMD-discordant monozygotic twins that were also detected in the non-twin cohort. Principal component analysis of the plasma-microRNA expression level demonstrated distinct 2 groups separated by MMD and healthy control in the twin- and non-twin cohorts. Of these, differential upregulations of hsa-miR-6722-3p/− 328-3p were validated in the plasma of MMD (absolute log2 expression fold change (logFC) > 0.26 for the twin cohort; absolute logFC > 0.26, p < 0.05, and q < 0.15 for the non-twin cohort). In MMD derived iPSECs, hsa-miR-6722-3p/− 328-3p showed a trend of up-regulation with a 3.0- or higher expression fold change. Bioinformatics analysis revealed that 41 target genes of miR-6722-3p/− 328-3p were significantly down-regulated in MMD derived iPSECs and were involved in STAT3, IGF-1-, and PTEN-signaling, suggesting a potential microRNA-gene expression interaction between circulating plasma and endothelial cells.ConclusionsOur MMD-discordant monozygotic twin-based study confirmed a novel circulating microRNA signature in MMD as a potential diagnostic biomarker minimally confounded by genetic heterogeneity. The novel circulating microRNA signature can contribute for the future functional microRNA analysis to find new diagnostic and therapeutic target of MMD.Electronic supplementary materialThe online version of this article (10.1186/s12920-018-0385-3) contains supplementary material, which is available to authorized users.

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Elevated Serum MicroRNA Let-7c in Moyamoya Disease

Cited by 12 publications

References 49 publications

Proposal for a Prospective Registry for Moyamoya Disease in Japan

Proposal for a Prospective Registry for Moyamoya Disease in Japan

Aberrant Promoter Hypomethylation of Sortilin 1: A Moyamoya Disease Biomarker

Circulating miRNome profiling in Moyamoya disease-discordant monozygotic twins and endothelial microRNA expression analysis using iPS cell line

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