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Middle Cerebral Artery Occlusion Allowing Reperfusion via Common Carotid Artery Repair in Mice
Published on: January 23, 2019
Identification of the lncRNA-miRNA‒mRNA regulatory network for middle cerebral artery occlusion-induced ischemic
Guixin Shi1, Dong He1, Hua Xiao1
1Department of Neurosurgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
Abstract:
Stroke known as a neurological disease has significant rates of disability and mortality. Middle cerebral artery occlusion (MCAO) models in rodents is crucial in stroke research to mimic human stroke. Building the mRNA and non-conding RNA network is essential for preventing MCAO-induced ischemic stroke occurrence. Herein, genome-wide mRNA, miRNA, and lncRNA expression profiles among the MCAO group at 3 h, 6 h, and 12 h after surgery and controls using high-throughput RNA sequencing. We detected differentially expressed mRNAs (DE-mRNAs), miRNAs (DE-miRNAs), and lncRNAs (DE-lncRNAs) between the MCAO and control groups. In addition, biological functional analyses were conducted, including GO/KEGG enrichment analysis, and protein-protein interaction analysis (PPI). GO analysis indicated that the DE-mRNAs were mainly enriched in several important biological processes as lipopolysaccharide, inflammatory response, and response to biotic stimulus. The PPI network analysis revealed that the 12 DE-mRNA target proteins showed more than 30° with other proteins, and the top three proteins with the highest node degree were Alb, IL-6, and TNF. In the DE-mRNAs, we found the mRNA of Gp6 and Elane interacting with two miRNAs (novel_miR_879 and novel_miR_528) and two lncRNAs (MSTRG.348134.3 and MSTRG.258402.19). As a result of this study, a new perspective can be gained into the molecular pathophysiology leading to the formation of MCAO. The mRNA-miRNA‒lncRNA regulatory networks play an important role in MCAO-induced ischemic stroke pathogenesis and could be applied to the treatment and prevention of ischemic stroke in the future.
Insights
Investigating middle cerebral artery occlusion (MCAO) in rodents reveals key mRNA, miRNA, and lncRNA networks. These molecular pathways are crucial for understanding and potentially treating ischemic stroke.
Area of Science:
- Neuroscience
- Molecular Biology
- Genomics
Background:
- Stroke is a leading cause of disability and mortality.
- Rodent models, specifically middle cerebral artery occlusion (MCAO), are vital for stroke research.
- Understanding molecular networks is key to preventing MCAO-induced ischemic stroke.
Purpose of the Study:
- To profile genome-wide mRNA, miRNA, and lncRNA expression in a rodent MCAO model.
- To identify differentially expressed genes and non-coding RNAs at various time points post-MCAO.
- To elucidate the regulatory networks involved in MCAO pathogenesis.
Main Methods:
- High-throughput RNA sequencing was used to analyze gene expression profiles.
- Differentially expressed mRNAs, miRNAs, and lncRNAs were detected.
- Gene Ontology (GO), KEGG pathway, and protein-protein interaction (PPI) analyses were performed.
Main Results:
- Significant differences in mRNA, miRNA, and lncRNA expression were observed between MCAO and control groups.
- GO analysis highlighted enrichment in inflammatory response pathways.
- PPI network analysis identified key proteins like Alb, IL-6, and TNF; identified interactions between specific mRNAs, miRNAs, and lncRNAs.
Conclusions:
- The study provides novel insights into the molecular pathophysiology of MCAO.
- mRNA-miRNA-lncRNA regulatory networks are implicated in ischemic stroke pathogenesis.
- These findings may offer future therapeutic targets for stroke prevention and treatment.

