Abstract
Hippocampal sclerosis (HS) is the most common surgical pathology associated with temporal lobe epilepsy (TLE). However, the cause of TLE with or without HS remains unknown. Our current study aimed to illustrate the essential molecular mechanism that is potentially involved in the pathogenesis of TLE-HS and to shed light on the transcriptional changes associated with hippocampal sclerosis. Compared to no-HS group, 341 mRNA transcripts and 131 circRNA transcripts were differentially expressed in ILAE type 1 group. The raw sequencing data have been deposited into sequence-read archive (SRA) database under accession number PRJNA699348.Gene Ontology analysis demonstrated that the dysregulated genes were associated with the biological processes of vesicle-mediated transport. Enrichment analysis demonstrated that dysregulated genes were involved mainly in the MAPK signal pathway. Subsequently, A total of 441 known or predicted interactions were formed among DEGs, and the most important module was detected in the PPI network using the MCODE plug-in. There were mainly four functional modules enriched: ER to Golgi transport vesicle membrane, Basal transcription factors, GABA-gated chloride ion channel activity, CENP-A containing nucleosome assembly. A circRNA-mRNA co-expression network was constructed including 5 circRNAs(hsa_circ_0025349, hsa_circ_0002405, hsa_circ_0004805, hsa_circ_0032254, and hsa_circ_0032875) and three mRNAs (FYN, SELENBP1, and GRIPAP1) based on the normalized mRNA signal intensities. This is the first to report the circRNAs and mRNAs expression profile of surgically resected hippocampal tissues from TLE patients of ILAE-1 and no-HS, and these results may provide new insight into the transcriptional changes associated with this pathology.
Highlights
Circular RNAs are a unique type of non-coding RNAs
temporal lobe epilepsy (TLE) is the most common form of drug-refractory epilepsy and surgery is the most effective therapy for this condition. Hippocampus in these patients often shows hippocampal sclerosis, a hallmark pathophysiological abnormality, which is characterized by segmental pyramidal cell loss and astrogliosis
In 2013, the International League Against Epilepsy (ILAE) developed a consensus classification system based on the qualitative histopathologic assessment of hippocampal subfields
Summary
Circular RNAs (circRNAs) are a unique type of non-coding RNAs. Unlike normal linear RNAs, their 3’-end of an exon is spliced to the 5’-end of an upstream exon resulting in a circular RNA molecular, which makes them more stable and conserved. A single can bind to several microRNAs (miRNAs) and suppress downstream target genes, resulting in gene suppression. This inhibition function is called a “sponge effect”. Several studies focused on differentially expressed circRNAs and their function in epilepsy patients and animal models, suggesting circRNAs as potentially novel biomarkers or therapeutic targets in this disease. We examined the expression profile of circRNAs in HS ILAE type 1 and no-HS type patients with TLE via next-generation sequencing analysis in a Chinese population. We performed an integrated analysis of circRNAs and mRNAs expression to discover novel key components and pathways involved in TLE-HS. This study may provide molecular information based on pathogenesis in Type 1 TLE patients
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