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Updated: Jul 19, 2025
Digital PCR for Quantifying Circulating MicroRNAs in Acute Myocardial Infarction and Cardiovascular Disease
Published on: July 3, 2018
Importance of microRNAs by mRNA-microRNA integration analysis in acute ischemic stroke patients
Hideaki Kanki1, Hisatake Matsumoto2, Yuki Togami2
1Department of Neurology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
Objects:
The roles of mRNA and microRNA (miRNA) are well known in many diseases, including ischemic stroke; thus, integration analysis using mRNA and miRNA is important to elucidate pathogenesis. However, their contribution, especially that of miRNA-targeted mRNA, to the severity of acute ischemic stroke remains unclear. Therefore, we examined mRNA and miRNA integration analysis targeted for acute ischemic stroke to clarify the pathway related to acute stroke severity.
Material And Methods:
We performed Ingenuity Pathway Analysis (IPA) using RNA extracted from the whole blood of four healthy controls, six minor acute ischemic stroke patients (MS; National Institutes of Health Stroke Scale [NIHSS] < 8), and six severe acute ischemic stroke patients (SS; NIHSS ≥ 8) on admission. mRNA and miRNA were measured using RNA sequencing and RNA expression variation; canonical pathway analysis (CPA) and upstream regulator analyses were performed.
Results:
Acute ischemic stroke patients demonstrated different RNA expressions to healthy controls. Compared to MS patients, in the SS patients, 1222 mRNA, 96 miRNA, and 935 miRNA-targeted mRNA expressions were identified among differentially expressed RNA expressions (p<0.05, |log2 fold change| >1.1). CPA by IPA using mRNAs or miRNA-targeted mRNAs showed that macrophage-stimulating protein (MSP)-recepteur d'origine nantais (RON) signaling was mostly activated in SS patients compared to in MS patients. In addition, upstream regulator analysis in IPA showed that most mRNAs located upstream are miRNAs.
Conclusions:
In severe acute stroke, integration of mRNA and microRNA analysis showed activated MSP-RON signaling in macrophages, and multiple miRNAs comprehensively controlled the overall pathophysiology of stroke.
Insights
Integrating messenger RNA (mRNA) and microRNA (miRNA) analysis reveals activated macrophage-stimulating protein (MSP)-RON signaling in severe acute ischemic stroke. This study clarifies pathways influencing stroke severity, highlighting miRNA's role in disease pathophysiology.
Area of Science:
- Biochemistry
- Genetics
- Neuroscience
Background:
- Messenger RNA (mRNA) and microRNA (miRNA) play crucial roles in various diseases, including ischemic stroke.
- Understanding the integrated roles of mRNA and miRNA is vital for elucidating disease pathogenesis.
- The specific contribution of miRNA-targeted mRNA to acute ischemic stroke severity requires further investigation.
Purpose of the Study:
- To investigate mRNA and miRNA integration analysis in acute ischemic stroke.
- To clarify the pathways associated with acute stroke severity.
- To identify the role of miRNA-targeted mRNA in stroke pathogenesis.
Main Methods:
- RNA sequencing and expression variation analysis were performed on whole blood samples.
- Ingenuity Pathway Analysis (IPA) was utilized for pathway and upstream regulator analyses.
- Patients were categorized into minor stroke (MS) and severe stroke (SS) groups based on NIHSS scores.
Main Results:
- Significant differences in RNA expression were observed between acute ischemic stroke patients and healthy controls.
- Severe stroke patients exhibited distinct expression patterns of mRNA, miRNA, and miRNA-targeted mRNA compared to minor stroke patients.
- Macrophage-stimulating protein (MSP)-RON signaling was identified as predominantly activated in severe stroke patients, with upstream regulators being primarily miRNAs.
Conclusions:
- Integrated mRNA and miRNA analysis in severe acute stroke revealed activated MSP-RON signaling in macrophages.
- Multiple miRNAs were found to comprehensively regulate the pathophysiology of acute ischemic stroke.
- This study provides insights into the molecular mechanisms underlying stroke severity.
