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Published on: June 20, 2025
Characterization of Dysregulated miRNA in Peripheral Blood Mononuclear Cells from Ischemic Stroke Patients
Marpe Bam1, Xiaoming Yang1, Souvik Sen2
1Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC, 29209, USA.
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.
Insights
Epigenetic regulation via microRNAs (miRNAs) is implicated in ischemic stroke (IS). This study found specific miRNA alterations in IS patients' blood cells, suggesting their role in immune system changes during stroke.
Area of Science:
- Epigenetics and Molecular Biology
- Neuroscience
- Immunology
Background:
- Epigenetic modifications, including microRNAs (miRNAs), are increasingly recognized for their role in ischemic stroke (IS) pathophysiology.
- miRNAs are small non-coding RNAs that regulate gene expression and are implicated in various clinical disorders, including IS.
Purpose of the Study:
- To investigate the microRNA (miRNA) profile in peripheral blood mononuclear cells (PBMCs) of IS patients.
- To compare miRNA expression in IS patients with stroke-free controls to identify dysregulated miRNAs associated with IS.
Main Methods:
- Blood samples were collected from 20 IS patients and 19 healthy controls.
- miRNA microarray analysis was performed on RNA extracted from PBMCs.
- Ingenuity Pathway Analysis (IPA) and molecular interactive network analysis were used to identify pathways and targets.
Main Results:
- 117 miRNAs showed a fold change of at least ±1.5, with 29 significantly altered (p <0.05).
- IPA revealed that dysregulated miRNAs are involved in conditions relevant to IS, such as organismal injury, hematological, and immunological diseases.
- Three miRNAs (hsa-miR-4656, -432, -503) were upregulated, and one (hsa-miR-874) was downregulated in all IS patients, targeting pro-inflammatory genes like STAT3 and interleukins.
Conclusions:
- Significant dysregulation of miRNAs was observed in the PBMCs of IS patients.
- These findings provide evidence for the involvement of altered miRNA expression in the immune system during IS pathophysiology.
- The identified miRNAs represent potential biomarkers and therapeutic targets for ischemic stroke.
