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

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.

miR-137 prevents inflammatory response, oxidative stress, neuronal injury and cognitive impairment via blockade of Src-mediated MAPK signaling pathway in ischemic stroke

“…MicroRNAs (miRNAs) regulate cellular pathways in a variety of clinical disorders, including ischemic stroke [7]. miR-137 is enriched in the brain and negatively regulates cell proliferation and accelerates the neuronal differentiation of embryonic neural stem cells [8].…”

Increased serum exosomal miR-134 expression in the acute ischemic stroke patients

“…Exosomal miRNAs establish the communication between cell-to-cell and are involved in regulating different biological processes via modulating the expression of target genes. Notably, the critical role of exosomal miRNAs in the development of stroke is emerging [ 17 , 19 , 25 ]. Recent study showed that the plasma exosomal miR-422a and miR-125b-2-3p were potential blood-base biomarkers for monitoring and diagnosing of IS patients [ 26 ].…”

Inflammatory Responses Induced by the Rupture of Intracranial Aneurysms Are Modulated by miRNAs

“…Bam et al investigated IS patients in the first 48 h and found several miRNAs to be dysregulated that are common in our RAA group, including hsa-miR-199b-3p, − 223, −30e, − 503, and − 550*. Among the top pathways enriched for regulated miRNAs were those related to cancer, hematological, and immunological diseases [15]. Additionally, Jickling et al analyzed miRNA expression in acute IS patients and found 8 differentially expressed miRNAs that potentially regulate genes in pathways associated with inflammatory/immune responses [16].…”