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Cerebrospinal Fluid MicroRNA Profiling Using Quantitative Real Time PCR
Published on: January 22, 2014
Circulating mRNA and microRNA profiling analysis in patients with ischemic stroke
Sujuan Sun1, Litao Li1, Lipeng Dong1
1Department of Neurology, Hebei General Hospital, Shijiazhuang, Hebei 050050, P.R. China.
Abstract:
To provide insight into molecular diagnosis and individualized treatment of ischemic stroke (IS), several available datasets in IS were analyzed to identify the differentially expressed genes and microRNAs (miRNAs). Series matrix files from GSE22255 and GSE16561 (mRNA profiles), a well as GSE110993 (miRNA profile) were downloaded from the Gene Expression Omnibus database. System‑level clustering was performed with GeneCluster 3.0 software, and gene annotation and pathway enrichment were performed with gene ontology analysis and Database for Annotation, Visualization and Integrated Discovery software. For a protein‑protein interaction (PPI) network, Biological General Repository for Interaction Datasets and IntAct interaction information were integrated to determine the interaction of differentially expressed genes. The selected miRNA candidates were imported into the TargetScan, miRDB and miRecords databases for the prediction of target genes. The present study identified 128 upregulated and 231 downregulated genes in female stroke patients, and 604 upregulated and 337 downregulated genes in male stroke patients compared with sex‑ and age‑matched controls. The construction of a PPI network demonstrated that male stroke patients exhibited YWHAE, CUL3 and JUN as network center nodes, and in female patients CYLD, FOS and PIK3R1 interactions were the strongest. Notably, these interactions are mainly involved in immune inflammatory response, apoptosis and other biological pathways, such as blood coagulation. Female and male upregulated genes were cross‑validated with another set of Illumina HumanRef‑8 v3.0 expression beadchip (GSE16561). Functional item association networks, gene function networks and transcriptional regulatory networks were successfully constructed, and the relationships between miRNAs and target genes were successfully predicted. The present study identified a number of transcription factors, including DEFA1, PDK4, SDPR, TCN1 and MMP9, and miRNAs, including miRNA (miR)‑21, miR‑143/145, miR‑125‑5p and miR‑122, which may serve important roles in the development of cerebral stroke and may be important molecular indicators for the treatment of IS.
Insights
This study identified key genes and microRNAs (miRNAs) involved in ischemic stroke (IS) by analyzing gene expression data. These findings offer potential molecular indicators for diagnosing and treating IS.
Area of Science:
- Genomics and Molecular Biology
- Neuroscience
- Biomedical Informatics
Background:
- Ischemic stroke (IS) poses a significant health challenge, necessitating advancements in molecular diagnosis and personalized treatment strategies.
- Understanding the molecular underpinnings of IS is crucial for developing targeted therapies.
Purpose of the Study:
- To identify differentially expressed genes and microRNAs (miRNAs) in ischemic stroke (IS) patients.
- To elucidate molecular pathways and interactions involved in IS pathogenesis.
- To discover potential molecular indicators for IS diagnosis and treatment.
Main Methods:
- Downloaded and analyzed mRNA and miRNA expression profiles from Gene Expression Omnibus (GEO) datasets (GSE22255, GSE16561, GSE110993).
- Performed system-level clustering, gene ontology analysis, and pathway enrichment analysis.
- Constructed protein-protein interaction (PPI) networks and predicted miRNA-target gene interactions using bioinformatics databases.
Main Results:
- Identified sex-specific differentially expressed genes in IS patients compared to controls.
- Revealed distinct network center nodes (YWHAE, CUL3, JUN in males; CYLD, FOS, PIK3R1 in females) in PPI networks.
- Highlighted the involvement of immune inflammatory response, apoptosis, and blood coagulation pathways.
- Identified key transcription factors (e.g., DEFA1, MMP9) and miRNAs (e.g., miR-21, miR-143/145) potentially crucial for IS development and treatment.
Conclusions:
- The study identified significant molecular players, including specific genes and miRNAs, implicated in the pathogenesis of ischemic stroke.
- These identified molecules may serve as valuable biomarkers for the molecular diagnosis and individualized treatment of IS.
- Further research into these identified factors could pave the way for novel therapeutic strategies for IS.

