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Network and Pathway-Based Analysis of Single-Nucleotide Polymorphism of miRNA in Temporal Lobe Epilepsy

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Abstract

Temporal lobe epilepsy (TLE) is a complex disease with its pathogenetic mechanism still unclear. Single-nucleotide polymorphisms (SNPs) of miRNA (miRSNPs) are SNPs located on miRNA genes or target sites of miRNAs, which have been proved to be associated with neuropsychic disease development by interfering with miRNA-mediated regulatory function. In this study, we integrated TLE–related risk genes and risk pathways multi-dimensionally based on public data resources. Furthermore, we systematically screened candidate functional miRSNPs for TLE and constructed a TLE-associated pathway-based miRSNP switching network, which included 92 miRNAs that target 12 TLE risk pathways. Moreover, we dissected thoroughly the correlation between 5 risk genes of 4 risk pathways and TLE development. Additionally, the biological function of several candidate miRSNPs were validated by luciferase reporter assay. In silico approach facilitates to select potential “miRSNP-miRNA-risk gene-pathway” axis for experimental validation, which provided new insights into the mechanism of miRSNPs as potential genetic risk factors of TLE.

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Funding

This study was supported financially by Omics-based precision medicine of epilepsy being entrusted by Key Research Project of the Ministry of Science and Technology of China (No. 2016YFC0904400), the National Natural Science Foundation of China (No. 81671299 to B.X and No. 81401078 to H.Y.L), the Science and Technology Department Funds of Hunan Province Key Project (No. 2016JC2057 to B.X. and No. 2018JJ3822 to H.Y.L), and Independent Exploration and Innovation project for postgraduate of Central South University (No. 2018zzts248 to W.B.X).

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Authors and Affiliations

  1. Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, China

    Wenbiao Xiao, Zhaohui Luo, Lili Long, Na Deng, Hongyu Long & Bo Xiao

  2. Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China

    Yanhao Wu

  3. Department of Neurology, the Second Affiliated Hospital, Harbin Medical University, Harbin, 150081, China

    Jianjian Wang

  4. College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China

    Shangwei Ning

  5. Department of Geriatrics, Second Xiangya Hospital, Central South University, Changsha, 410011, China

    Yi Zeng

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  1. Wenbiao Xiao
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Xiao, W., Wu, Y., Wang, J. et al. Network and Pathway-Based Analysis of Single-Nucleotide Polymorphism of miRNA in Temporal Lobe Epilepsy. Mol Neurobiol 56, 7022–7031 (2019). https://doi.org/10.1007/s12035-019-1584-4

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