Identification of novel circulatory microRNA signatures linked to patients with ischemic stroke


Biomarkers might be useful in early detection of diseases such as stroke, cancer, diabetes. Identification of biomarkers may also contribute to a better understanding of the etiologies and mechanisms underlying particular diseases, such as stroke.

Recent discoveries have revealed that microRNAs (miRNAs) can detect changes in bodily organs, including brain, that may lead to ischemic stroke (IS). MiRNAs are important posttranscriptional regulators that connect with multiple target messenger RNAs to regulate target genes. MiRNAs have also been found to be important regulators of leukocyte gene expression in acute IS cases. Many studies showed that miRNAs altered after central nervous system injury moderate processes that stimulate neuronal death with inflammation, apoptosis and oxidative stress. Furthermore, miRNAs can act as biomarkers of secondary brain damage. Studies also suggested that peripheral blood miRNAs could be developed as diagnostic and prognostic biomarkers of IS, as well as serving as innovative targets in the treatment of this disease. Current clinical approaches to the diagnosis and prognosis of stroke are restricted to radiological imaging, with limited availability and high cost. Therefore, new methods for the diagnosis and development of could benefit from new IS biomarkers.

The purpose of this study is to identify circulatory miRNAs that may serve as early peripheral biomarkers of IS. MiRNAs expression levels were measured in IS serum samples and healthy controls using Illumina deep sequencing. Differentially expressed miRNAs were further validated using SYBR-green based quantitative real-time PCR assay (qRT-PCR) in postmortem IS brains, lymphoblastoid IS cell lines, OGD/R treated human and mouse neuroblastoma cells, and mouse models of hypoxia and ischemia (HI) induced stroke.

A total of 4,656 miRNAs were differentially expressed in IS serum samples relative to healthy controls. Out of 4,656 miRNAs, 272 were found to be significantly deregulated in IS patients.

Interestingly, researchers found several novel miRNAs in IS patients. Further analyses revealed that some candidate miRNAs and their target genes were involved in the regulation of stroke. MiRNAs identified in this study could potentially be used as IS biomarkers and for the development of novel therapeutic approaches. Further studies are necessary to better understand miRNAs-regulated stroke cellular changes.

Click here to access the publication abstract available on the PubMed website:

PMID: 29701837

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