Journal
MOLECULAR NEUROBIOLOGY
Volume 56, Issue 10, Pages 7022-7031Publisher
SPRINGER
DOI: 10.1007/s12035-019-1584-4
Keywords
Temporal lobe epilepsy (TLE); Risk gene; miRSNP; Pathway; Network
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Funding
- Omics-based precision medicine of epilepsy being entrusted by Key Research Project of the Ministry of Science and Technology of China [2016YFC0904400]
- National Natural Science Foundation of China [81671299, 81401078]
- Science and Technology Department Funds of Hunan Province Key Project [2016JC2057, 2018JJ3822]
- Independent Exploration and Innovation project for postgraduate of Central South University [2018zzts248]
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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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