Abstract
Objectives This study is aimed at exploring the relationships between miRNAs and mRNAs and to characterize their biological functions in temporal lobe epilepsy (TLE). Methods Novel clinical significant miRNAs and target genes and their potential underlying mechanisms have been discovered and explored by mining miRNAs and mRNA expression data of TLE patients using various bioinformatics methods. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to validate the bioinformatic analysis results. Results A total of 6 dysregulated miRNAs and 442 differentially expressed genes (DEGs) related to TLE were obtained from GEO database (GSE114701 and GSE127871 datasets). A protein-protein interaction (PPI) network containing the 442 DEGs was established. mRNA response elements from the 6 dysregulated miRNAs were predicted using the miRDB and TargetScan bioinformatic tools. By merging the identified targets of the dysregulated miRNAs and the 247 downregulated DEGs, a miRNA-mRNA network was constructed revealing the interaction of miR-484 with eight mRNAs (ABLIM2, CEP170B, CTD-3193O13.9, EFNA5, GAP43, PRKCB, FXYD7, and NCAN). A weighted correlation network analysis (WGCNA) based on the eight genes was established and demonstrated that these mRNAs, except FXYD7 and NCAN, were hub genes in the network. Gene Oncology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that the six hub genes were mainly involved in cellular-related biological functions and the neurotransmitter synapse pathway. The differences in expression levels of the miR-484 and the three hub genes (CTD-3193O13.9, EFNA5, and PRKCB) observed experimentally in TLE patients compared to those of healthy controls were consistent with the WGCNA prediction. Conclusion Our study suggests that understanding the miRNA-mRNA interactions will provide insights into the epilepsy pathogenesis. In addition, our results indicate that miR-484 may be a promising novel biomarker for TLE.
Highlights
Temporal lobe epilepsy (TLE) is the refractory epilepsy marked by spontaneous recurrent seizures and the leading cause of hippocampal sclerosis
By weighted correlation network analysis (WGCNA), we identified the key genes that are significantly associated with temporal lobe epilepsy (TLE) clinical features
A total of 442 differentially expressed genes (DEGs) were identified by comparing high seizure frequency (HSF) and low seizure frequency (LSF) hippocampus tissues from the GSE127871 dataset, with 195 and 247 DEGs being up- and downregulated, respectively
Summary
Temporal lobe epilepsy (TLE) is the refractory epilepsy marked by spontaneous recurrent seizures and the leading cause of hippocampal sclerosis. TLE is accountable for 50– 80% of all diagnosed refractory epilepsy cases and is divided mainly into medial temporal lobe epilepsy (MTLE) and lateral temporal lobe epilepsy (LTLE) [1]. TLE neuropsychiatric complications have been reported to affect 30–70% of patients, the most common of which are memory deficits [2] and cognitive impairment [3]. Epileptogenic zone surgery, and antiepileptic drugs have been applied for TLE therapy, the drug-resistant rate and neuropsychological impairment of TLE patients are still high [4]. Recent studies have shown some new insights about genetic and regulatory changes in the biological processes underlying TLE. The precise pathogenesis and effective biomarkers involved in the TLE epileptogenesis
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