Differential Expression Analysis of miRNAs and mRNAs in Epilepsy Uncovers Potential Biomarkers

Abstract

Abstract Epilepsy is a neurological disease defined by episodes of synchronous convulsions. Recently, miRNAs have been proven as promising biomarkers for multiple ailments like tumors and neurodegenerative disorders; their role in epilepsy is still unclear. This study aimed to understand the involvement of miRNAs in the disease and to detect the potential biomarkers for the treatment of epilepsy. RNA transcripts, and miRNA from brain tissue and plasma small extracellular vesicle samples of epileptogenic patients from 6 different studies downloaded from the NCBI sequence read archive (SRA) were analyzed with particular interest in genes that might be involved in epilepsy. Alignment of transcripts to hg38 was done using HISAT2 and the raw counts were generated using HTseq-count. miRNA genes were identified using miRDeep2. EdgeR and GEO2 were used to identify DEGs for both mRNA and miRNA datasets. Finally, TargetScan web tool was used to predict potentially significantly expressed mRNA target genes using the identified miRNA genes. Analysis of these datasets revealed target genes in epilepsy and their associated miRNAs. SIX4 and KCTD7 were under-expressed in epileptogenic zones of the brain compared to the irritative zone. CABP1, SLC20A1 and SLC35G1 were under-expressed in brain tissues. Hsa-miR-27a-3p was identified as a regulator of CABP1 expression, hsa-let-7b-5p regulates SLC20A1 while hsa-miR-15a-5p and hsa-miR-195-5p are regulators for SLC35G1. These observations highlight the importance of miRNAs as novel biomarkers of epilepsy. Understanding and controlling these regulatory interactions may help to define potential therapies for epilepsy. This would also help to better understand miRNA-mediated gene regulation in epilepsy.