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Characterization of Dysregulated miRNA in Peripheral Blood Mononuclear Cells from Ischemic Stroke Patients

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Abstract

Epigenetic modification may play an important role in pathophysiology of ischemic stroke (IS) risk. MicroRNAs (miRNAs), which constitute one of the modes of epigenetic regulation, have been shown to be associated with a number of clinical disorders including IS. The purpose of this study was to investigate the miRNA profile in the peripheral blood mononuclear cells (PBMCs) of IS patients and compare it with stroke-free controls. Blood samples were obtained from 19 healthy age-gender-race matched individuals who served as controls to 20 IS patients. miRNA microarray analysis with RNA from PBMCs was performed and significantly dysregulated miRNAs common among IS patients were identified. We identified 117 miRNAs with linear fold values of at least ±1.5, of which, 29 were significantly altered (p value <0.05). Ingenuity Pathway Analysis (IPA) indicated a role for the dysregulated miRNAs in conditions relevant to IS (e.g., organismal injury and abnormalities, hematological disease and immunological disease). Pro-inflammatory genes like STAT3, interleukin (IL) 12A, and IL12B were some of the highly predicted targets for the dysregulated miRNAs. Notably, we further identified three common and significantly upregulated miRNAs (hsa-miR-4656, -432, -503) and one downregulated miRNA (hsa-miR-874) among all IS patients. Molecular interactive network analysis revealed that the commonly dysregulated miRNAs share several targets with roles relevant to IS. Altogether, we report dysregulation of miRNAs in IS PBMCs and provide evidence for their involvement in the immune system alteration during IS pathophysiology.

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Acknowledgements

This study is supported in part by the SC Smart State Funds, National Institutes of Health grants P01AT003961, R01AT006888, R01ES019313, R01MH094755, AI29788, and P20GM103641 to PN and MN.

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Authors and Affiliations

  1. Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC, 29209, USA

    Marpe Bam, Xiaoming Yang, Elizabeth E. Zumbrun, Prakash S. Nagarkatti & Mitzi Nagarkatti

  2. Department of Neurology, University of South Carolina School of Medicine, Columbia, SC, 29203, USA

    Souvik Sen, Lauren Dennis & Mitzi Nagarkatti

  3. Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, 29206, USA

    Jiajia Zhang

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  1. Marpe Bam
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Correspondence to Mitzi Nagarkatti.

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All procedures performed in studies involving human participants were approved by the Institutional Review Board of the University of South Carolina and obtained written consent from all participants/subjects.

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Bam, M., Yang, X., Sen, S. et al. Characterization of Dysregulated miRNA in Peripheral Blood Mononuclear Cells from Ischemic Stroke Patients. Mol Neurobiol 55, 1419–1429 (2018). https://doi.org/10.1007/s12035-016-0347-8

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