Abstract
Temporal lobe epilepsy (TLE) is one of the most common types of intractable epilepsy, characterized by hippocampal neuron damage and hippocampal sclerosis. Long noncoding RNAs (lncRNAs) have been increasingly recognized as posttranscriptional regulators. However, their expression levels and functions in TLE remain largely unknown. In the present study, TLE rat model is used to explore the expression profiles of lncRNAs in the hippocampus of epileptic rats using microarray analysis. Our results demonstrate that H19 is the most pronouncedly differentiated lncRNA, significantly upregulated in the latent period of TLE. Moreover, the in vivo studies using gain- and loss-of-function approaches reveal that the overexpression of H19 aggravates SE-induced neuron apoptosis in the hippocampus, while inhibition of H19 protects the rats from SE-induced cellular injury. Finally, we show that H19 might function as a competing endogenous RNA to sponge microRNA let-7b in the regulation of cellular apoptosis. Overall, our study reveals a novel lncRNA H19-mediated mechanism in seizure-induced neural damage and provides a new target in developing lncRNA-based strategies to reduce seizure-induced brain injury.
Highlights
Temporal lobe epilepsy (TLE) is the most common type of acquired epilepsy in adults, of which one-third of patients are refractory to medications[1]
To explore the expression profiles of long noncoding RNAs (lncRNAs) and mRNAs related to epileptogenesis, hippocampi from epilepsy rat model at 1 day post-status epilepticus (SE) were used for microarray analysis
The threshold for differential expression was set as fold change >1.2 for lncRNAs and >1.5 for mRNAs
Summary
Temporal lobe epilepsy (TLE) is the most common type of acquired epilepsy in adults, of which one-third of patients are refractory to medications[1]. (see figure on previous page) Fig. 1 Differential expression of mRNAs and long noncoding RNAs (lncRNAs) in rat hippocampus after status epilepticus (SE). C Gene ontology (GO) and d pathway analysis of the differentially expressed genes. The horizontal axis represents the gene expression levels after Log-normalized transformation and the vertical axis represents the GO names or pathways. This co-expression network consists of H19 (center) and its 54 co-expression protein-coding genes. Protein-coding genes are represented by nodes, of which red nodes represent upregulated genes and blue nodes represent downregulated genes. The solid lines indicate positive correlations, and the dashed lines indicate negative correlations functions of long noncoding RNAs (lncRNAs) attract increasing attention. To date, few studies have explored the functions of lncRNAs in TLE. Evidences have been presented that H19 can act as either an oncogene[13] or tumor suppressor[14,15]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
