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Circulating MicroRNA Profiling Identifies Distinct MicroRNA Signatures in Acute Ischemic Stroke and Transient Ischemic Attack Patients

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submitted on 2024-07-02, 10:00 and posted on 2024-07-02, 10:02 authored by Salman M. Toor, Eman K. Aldous, Aijaz Parray, Naveed Akhtar, Yasser Al-Sarraj, Essam M. Abdelalim, Abdelilah Arredouani, Omar El-Agnaf, Paul J. Thornalley, Sajitha V. Pananchikkal, Ghulam Jeelani Pir, Raheem Ayadathil, Ashfaq Shuaib, Nehad M. Alajez, Omar M. E. Albagha

Transient ischemic attack (TIA) refers to a momentary neurologic deficit caused by focal cerebral, spinal or retinal ischemic insult. TIA is associated with a high risk of impending acute ischemic stroke (AIS), a neurologic dysfunction characterized by focal cerebral, spinal or retinal infarction. Understanding the differences in molecular pathways in AIS and TIA has merit for deciphering the underlying cause for neuronal deficits with long-term effects and high risks of morbidity and mortality. In this study, we performed comprehensive investigations into the circulating microRNA (miRNA) profiles of AIS (n = 191) and TIA (n = 61) patients. We performed RNA-Seq on serum samples collected within 24 hrs of clinical diagnosis and randomly divided the study populations into discovery and validation cohorts. We identified a panel of 11 differentially regulated miRNAs at FDR < 0.05. Hsa-miR-548c-5p, -20a-5p, -18a-5p, -484, -652-3p, -486-3p, -24-3p, -181a-5p and -222-3p were upregulated, while hsa-miR-500a-3p and -206 were downregulated in AIS patients compared to TIA patients. We also probed the previously validated gene targets of our identified miRNA panel to highlight the molecular pathways affected in AIS. Moreover, we developed a multivariate classifier with potential utilization as a discriminative biomarker for AIS and TIA patients. The underlying molecular pathways in AIS compared to TIA may be explored further in functional studies for therapeutic targeting in clinical translation.

Other Information

Published in: International Journal of Molecular Sciences
License: https://creativecommons.org/licenses/by/4.0/
See article on publisher's website: https://dx.doi.org/10.3390/ijms24010108

Additional institutions affiliated with: Qatar Genome Programme (2015-2024), Qatar Precision Health Institute.

Funding

Hamad Medical Corporation (15304/15).

History

Language

  • English

Publisher

MDPI

Publication Year

  • 2022

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License.

Institution affiliated with

  • Hamad Bin Khalifa University
  • College of Health and Life Sciences - HBKU
  • Qatar Biomedical Research Institute - HBKU
  • Cancer Research Center - QBRI
  • Diabetes Research Center - QBRI
  • Neurological Disorders Research Center - QBRI
  • Hamad Medical Corporation
  • Academic Health System - HMC
  • Neuroscience Institute - HMC
  • Hamad General Hospital - HMC