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Bioinformatics Analysis of Microarray Profiling Identifies That the miR-203-3p Target Ppp2ca Aggravates Seizure Activity in Mice

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Abstract

This study aimed to identify key genes (microRNA and messenger RNA (mRNA)) and associated signaling-regulated pathways in a drug-induced epilepsy model in mice by microarray profiling. The related microarray dataset of seizures was obtained from the NCBI Gene Expression Omnibus database (GEO), and differentially expressed genes (DEGs) between two control samples or multi-treated samples and samples were analyzed using the statistical software R. To identify the expected function of DEGs, Gene Set Enrichment Analysis (GSEA) was utilized to conduct Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The interaction relationship between microRNAs (miRNAs) and mRNAs in normal and epilepsy mouse models was identified using Cytoscape software. TargetScan7.1 was applied to determine the binding sites of DEGs. The dual-luciferase assay was used to verify the target relationship between miRNA and mRNA. Four miRNAs were identified as differentially expressed genes in both 24-h and 28-day status epilepticus (SE)-treated samples. Ppp2ca expression in the mitogen-activated protein kinase (MAPK) signaling pathway was downregulated in the pilocarpine-induced SE mouse model. The expression of Ppp2ca was also downregulated in the kinase-induced SE model group compared with that in the untreated group and MAP kinase (MEK) inhibitor-treated group of mice. KEGG pathway analysis indicated that the MAPK signaling pathway was upregulated in the kinase-induced SE model group compared with that in both the untreated group and the MEK inhibitor-treated group of mice. miR-203 had a targeted relationship with Ppp2ca in both humans and mice. The miR-203-3p target Ppp2ca aggravates the seizures of the SE model in mice.

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Acknowledgements

We extend our sincere appreciation to the reviewers for their helpful comments on this article.

Funding

This work was supported by the Scientific Research Program of Health and Family Planning Commission of Shanxi Province (No. 201602027) and the Start-up Fund Program for Doctor of Changzhi Medical College (No. BS15004).

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Authors and Affiliations

  1. Department of Neurology, Changzhi People’s Hospital, Changzhi Medical College, No. 161 East Jiefang Road, Changzhi, 046000, Shanxi, China

    Lifang Zhang, Xuexue Ye & Lin Bian

  2. Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, 100069, China

    Yanran Li

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  1. Lifang Zhang
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  2. Yanran Li
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  4. Lin Bian
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Correspondence to Lifang Zhang.

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Zhang, L., Li, Y., Ye, X. et al. Bioinformatics Analysis of Microarray Profiling Identifies That the miR-203-3p Target Ppp2ca Aggravates Seizure Activity in Mice. J Mol Neurosci 66, 146–154 (2018). https://doi.org/10.1007/s12031-018-1145-8

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  • DOI: https://doi.org/10.1007/s12031-018-1145-8

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