Differential long non-coding RNA (lncRNA) profiles associated with hippocampal sclerosis in human mesial temporal lobe epilepsy

Objective: The aim of this study was to analyze the expression profiles of long non-coding RNA (lncRNAs) in human mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS) and to detect the functions of lncRNAs in epileptogenesis in MTLE. Materials and methods: We used microarray analysis to analyze the differential expression of lncRNAs and mRNAs in three hippocampal sclerosis and three normal hippocampus samples. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the microarrray results. A coding and non-coding gene co-expression network was constructed based on the correlation between the differential expression of lncRNAs and mRNAs. Gene ontology (GO) and pathway analyses were then performed to determine the potential roles of the differentially expressed mRNAs in the co-expression network. Lastly, to understand potential functions of lncRNAs in MTLE, cis-Mans-acting lncRNAs were predicted using bioinformatic analysis. Results: Compared with control hippocampus, 497 differentially expressed lncRNAs were identified in the hippocampal sclerosis samples, consisting of 294 up-regulated and 203 down-regulated lncRNAs (fold-change >2.0 or <-2.0, P<0.05). Similarly, 399 differentially expressed mRNAs were identified with 236 up-regulated and 163 down-regulated. There were 356 lncRNAs and 332 mRNAs in the non-coding and coding co-expression network, in which the highly enriched GO categories were related to the inflammatory response, and neuropeptide receptor activity. Nine pairs of lncRNAs and mRNAs (located within 10 kb of each other) were found to exert functional effects on epileptogenesis. Conclusion: Differential expression of lncRNAs of varying length and location were observed in human MTLE with hippocampal sclerosis. The dysregulated lncRNAs with co-dysregulated mRNAs in inflammatory response and neuropeptide receptor activity categories are predicted to play roles in epileptogenesis in MTLE. LncRNA RP11-414J4 may contribute to epileptogenesis by targeting CPLX3.