Abstract
Objective With the growing incidence of ischemic stroke worldwide, there is an urgent need to identify blood biomarkers for ischemic stroke patients. Thus, our aim was to identify potential circulating microRNA (miRNA) as a potential biomarker and to explore its potential mechanism for ischemic stroke in rats. Methods The mRNA dataset GSE97537 and miRNA dataset GSE97532 were downloaded from the Gene Expression Omnibus (GEO) GSE97537 including 7 middle cerebral artery occlusion (MCAO) rat brain tissues and 5 sham-operated rat brain tissues GSE97532 including 6 MCAO rat blood samples and 3 sham-operated rat blood samples. Differentially expressed mRNAs and miRNAs with corrected p value ≤ 0.01 and fold change ≥2 or ≤0.05 were identified. To explore potential biological processes and pathways of differentially expressed mRNAs, functional enrichment analysis was performed. The target mRNAs of differentially expressed miRNAs were predicted using DNA Intelligent Analysis (DIANA)-microT tools. The target mRNAs and differentially expressed mRNAs were intersected. Results 1228 differentially expressed mRNAs in MCAO rat brain tissues were identified. Highly expressed mRNAs were mainly enriched in the inflammatory responses. Nine differentially expressed miRNAs were identified in MCAO rat blood samples. A total of 673 target mRNAs were predicted to significantly bind these differentially expressed miRNAs. Among them, 54 target mRNAs were differentially expressed in MCAO rat blood samples. Enrichment analysis results showed that these 54 target mRNAs were closely related to neurological diseases and immune responses. Among all miRNA-mRNA relationship, miR-3552-CASP3 interaction was identified, indicating that CASP3 might be mediated by miR-3552. Functional enrichment analysis revealed that CASP3 was involved in the apoptosis pathway, indicating that miR-3552 might participate in apoptosis by CASP3. Conclusion Our findings reveal that circulating miR-3552 shows promise as a potential biomarker for ischemic stroke in rats.
Highlights
Stroke is the third leading cause of death after heart disease and cancer, classified as ischemic (85%) and hemorrhagic (15%) [1]
Using the correlation coefficient matrix, we found the differences in transcription levels between 7 middle cerebral artery occlusion (MCAO) rat brain tissues and 5 sham-operated rat brain tissues (Figure 1)
We identified 1228 differentially expressed mRNAs with corrected p value ≤ 0.01 and fold change ≥2 or ≤0.05 between MCAO rat brain tissues and sham-operated rat brain tissues, including 829 up-regulated and 399 down-regulated mRNAs (Figure 2, Supplementary Table 3)
Summary
Stroke is the third leading cause of death after heart disease and cancer, classified as ischemic (85%) and hemorrhagic (15%) [1]. Ischemic stroke occurs when cerebral blood flow is interrupted, usually due to arterial thrombosis or embolism. Ischemic stroke poses a major threat to patient health and quality of life. The pathogenic mechanisms of ischemic stroke remain to be clarified, leading to an ideal clinical treatment [2, 3]. Understanding the molecular neuroinflammatory mechanism of ischemic stroke can significantly enhance the development of treatment. Prognostic blood biomarkers provide a novel strategy for the diagnosis and prognosis of stroke [4]. The diagnosis of ischemic stroke usually relies on computed tomography. The diagnostic value of blood biomarkers in ischemic stroke remains limited
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