Bioinformatic Analysis of Potential microRNAs in Ischemic Stroke
Introduction
Ischemic stroke represents one of the leading causes of serious long-term disability and mortality worldwide, which is characterized by cerebral ischemia.1, 2 Up to now, ischemic stroke is diagnosed based mainly on the results from clinical examination, computed tomography and magnetic resonance imaging, and blood protein analyses, and thrombolysis is the only efficacious treatment for ischemic stroke.3 Ischemic stroke is considered as a highly complex polygenic disease with multiple underlying risk factors, such as hypertension, atherosclerosis, type 2 diabetes, smoking, and alcohol consumption.4
MicroRNAs (miRNAs) can bind to their target mRNAs, resulting in degradation and/or translational repression of the transcript. The altered miRNA expression can exert effects on many target mRNAs and result in diverse functional consequences. Many studies have been carried out to show the vital role of miRNAs in the progression of cerebral ischemia. Moreover, growing evidence has suggested that alteration of miRNAs plays critical roles in the pathologies of ischemic stroke.5 It was reported that miRNA may play an important regulatory role in the early cell stress response to ischemia in the brain and in the immune system and vasculature.6 Previous studies indicated that miRNAs are dysregulated in the blood and brain of rodent ischemic stroke and human stroke patients.7, 8, 9 The significance of several miRNAs in ischemic brain damage has been evaluated. miR-15a is important in the pathogenesis of ischemic vascular injury.10 Downregulation of miR-497 can reduce infarct and improve neurological deficits.11 It has been shown that miR-210 is positively correlated with better prognosis in stroke patients.12 Even so, the specificity to acute stroke pathology has not been established.
The dysregulation of genes in ischemic stroke is most likely regulated by miRNA. Hence, additional study is required to better understand miRNAs and their regulation of genes and pathways involved in ischemic stroke. To investigate this issue, we performed an integrated analysis of the miRNA and mRNA expression profiles of ischemic stroke. Based on the miRNA–target pairs predicted, a global miRNA–target regulatory network was constructed, which may further explain the regulatory mechanism of miRNAs, provide novel targeted therapeutic strategies against the affected patients, and improve ischemic stroke outcome.
Section snippets
Dataset Collection
The Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo) served as a public repository for gene expression datasets,13 and it was used to obtain mRNA and miRNA expression profiling studies in ischemic stroke. The following keywords were used: ([“ischemia” {MeSH Terms} or ischemic {All Fields}] and [“stroke” {MeSH Terms} or stroke {All Fields}]) and “Homo sapiens” (porgn) and “gse” (Filter). Moreover, only the microarray studies were retained for further analysis. The basic
Differentially Expressed miRNAs and mRNAs in Ischemic stroke
According to inclusion criteria, 2 mRNA expression profiling studies (GSE22255 and GSE16561) and 1 miRNA expression profiling study (GSE55937) were obtained. In total, there were 68 normal samples and 83 patient samples, respectively (Table 1). After normalization of the original miRNA and mRNA expression data, we performed differentially expressed analysis between ischemic stroke and normal control samples. Finally, 16 miRNAs were regarded as significantly differentially expressed with P
Discussion
Endogenous circulating miRNAs are stable and have emerged as vital regulators in many physiological and pathological processes. Accumulating evidence has suggested that miRNAs have constituted excellent biomarkers for different human diseases.19 In the present study, we sought to scrutinize the effects of miRNAs by integrated analysis of 2 mRNA expression profiling and 1 miRNA expression profiling obtained from the GEO database. Based on the results from miRNA analysis, there were only 4
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2019, Life SciencesCitation Excerpt :Additionally, miR-145 could be involved in ischemic stroke by regulating the inflammatory response [10]. Both our previous study [11] and the present study found that miR-145 was significantly upregulated in the blood of patients with ischemic stroke compared to that of normal controls. Moreover, miR-145 mimetics improved the cell survival rate in the OGD model, while the miR-145 inhibitor decreased the cell survival rate, which suggested the protective effects of miR-145 for cell viability after ischemic stroke.
Differential MicroRibonucleic Acid Expression in Cardioembolic Stroke
2019, Journal of Stroke and Cerebrovascular DiseasesCitation Excerpt :Further investigation of these miRNA may reveal new mechanisms of regulation in response to cerebral injury. Our study identified 10 miRNAs that have not previously been associated with ischemic stroke (Table 2).3-8 MiRNAs miR-4531, miR-4756-3p, and miR-5584-3p were downregulated in patients with ischemic stroke.