Abstract
This study was aimed at investigating the differentially expressions of long noncoding RNAs (lncRNAs) and mRNAs in the brains of a middle cerebral artery occlusion/reperfusion (MCAO/R) group and a MCAO/R + 20(R)-Rg3 group. Biological enrichment analysis was performed, and a lncRNA-mRNA coexpression network was constructed, to reveal the targets and pathways of 20(R)-Rg3 involved in the regulation of cerebral ischemia-reperfusion injury (CIRI). The RNA-seq high-throughput sequencing method was employed to detect differentially-expressed genes between the groups, which were verified by RT-PCR. Functional enrichment analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed to explore the biological functions and relevant pathways. The coexpression network of the screened lncRNAs and mRNAs was built by using Cytoscape software. The results identified 77 upregulated lncRNAs, 162 downregulated lncRNAs, 66 upregulated mRNAs and 472 downregulated mRNAs in the MCAO/R + 20(R)-Rg3 group, compared with those in the MCAO/R group. GO enrichment analysis showed that the GO terms were mainly enriched in stimulation response, cellular response, and stress response. KEGG pathways were mainly related to the tumor necrosis factor (TNF), NF-κB, cytokine, and other receptor signaling pathways. In addition, the coexpression analysis between lncRNA and mRNA identified 314 nodes and 515 connections between 6 lncRNAs and 308 mRNAs, of which 511 were positive and 4 were negative. Among them, ENSRNOG-00000059555 was strongly correlated with AABR07001160.1. This study revealed multiple lncRNAs were involved in the neuroprotection of 20(R)-Rg3 against CIRI and thereby provided new insights into the use of 20(R)-Rg3 as a novel neuro protectant in ischemic stroke management.
Highlights
Ischemic stroke is recognized as one of the most prevalent neurological/strokerelated disorders worldwide with high rates of morbidity and disability
Our results demonstrated that multiple long noncoding RNAs (lncRNAs) are closely associated with the protective efficacy of 20(R)Rg3 in a middle cerebral artery occlusion/reperfusion (MCAO/R)-induced rat model and provide a novel treatment for neurological diseases related to ischemic stroke
Taking six lncRNAs as the core, the closer the surrounding mRNAs were, the higher the correlation was. Among these mRNAs with high correlation, we found that many genes could regulate neurons, such as prokinetin 2 (Prok2), growth/differentiation factor 3 (GDF3) and C-C chemokine ligand 20 (CCL20)
Summary
Ischemic stroke ( called cerebral infarction) is recognized as one of the most prevalent neurological/strokerelated disorders worldwide with high rates of morbidity and disability. It has been reported that ischemic stroke makes up to 70–85% of all strokes [1]. Cerebral ischemia-reperfusion injury (CIRI) is considered as a complicated pathophysiological condition of ischemic stroke involving excitotoxicity, inflammatory response, oxidative stress and apoptosis [2]. CIRI can activate macrophages and microglia, produce proinflammatory mediators such as tumor necrosis factor (TNF), the interleukin family cytokines, and adhesion molecules, increase leukocyte infiltration, and eventually lead to the apoptosis of neurons [4]. Long noncoding RNAs (lncRNAs), as new key regulators involved in nervous system diseases, have attracted increasing attention from researchers [5]
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