The mircoRNA expression profiles of human temporal lobe epilepsy in HS ILAE type 1

Temporal lobe epilepsy (TLE) is associated with neurodegeneration, often leading to hippocampal sclerosis (HS). The type 1 HS, which is characterized by severe neuronal cell loss and gliosis predominantly in regions CA1 and CA4, is the most common subtype and is associated with best prognosis according to ILAE classification system. MiRNAs are participate in the biological processes underlying many nervous system diseases including epilepsy. However, the miRNA expression profile of HS ILAE type 1 is not completely understood. A total of 14 patients were identified as having the ILAE subtype, as determined by NeuN immunohistochemistry (ILAE type 1=7; no-HS=7). Next-generation sequencing and reverse transcription polymerase chain reaction technology was used to validate the dysregulated miRNAs. Bioinformatics analysis of the predicted target gene was conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. In total, 1643 mature miRNAs were detected in this study, along with 5 miRNAs were upregulated and 2 miRNAs were downregulated expression in the type 1 group. Bioinformatics analysis showed that 1545 target genes were predicted using miRDB and Targetscan databases, and these predicted genes showed enrichment in the pathway associated with nucleic acid binding, intracellular and cellular macromolecule metabolic processes, and the PI3K-Akt signaling pathway. This study is the first to report the miRNA expression profile of HS ILAE type 1 compared with no-HS. These results provide new insights into the neuron loss pathology and offer fundamental evidence as to why there is a good prognosis among patients with type 1 HS. Overall design: MicroRNA profile of 3 hippocampus section of ILAE type I and No-HS type in each group were generated by next-generation sequencing, using Illumina Hiseq 2500 platform.

颞叶癫痫（Temporal lobe epilepsy, TLE）与神经退行性变密切相关，常引发海马硬化（hippocampal sclerosis, HS）。其中1型海马硬化以CA1、CA4区域显著的神经元丢失及胶质增生为主要特征，是最常见的HS亚型，且根据国际抗癫痫联盟（ILAE）分类系统，该亚型预后最佳。微小RNA（MicroRNAs, miRNAs）参与包括癫痫在内的多种神经系统疾病的病理生理过程，但目前对于ILAE 1型HS的miRNA表达谱仍未完全明确。本研究通过NeuN免疫组化鉴定，共纳入14例符合ILAE分型的患者，其中ILAE 1型HS组7例、无海马硬化（no-HS）组7例。采用二代测序技术与逆转录聚合酶链反应（reverse transcription polymerase chain reaction）对差异表达的miRNAs进行验证，并通过基因本体（Gene Ontology, GO）富集分析及京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）通路分析，对预测得到的靶基因开展生物信息学研究。本研究共检测到1643个成熟miRNAs，其中ILAE 1型HS组有5个miRNAs表达上调、2个miRNAs表达下调。通过miRDB和Targetscan数据库共预测得到1545个靶基因，生物信息学分析显示，这些靶基因显著富集于核酸结合、细胞内及细胞大分子代谢过程，以及PI3K-Akt信号通路中。本研究首次报道了与无海马硬化组相比的ILAE 1型HS的miRNA表达谱，研究结果为神经元丢失的病理机制提供了新的见解，并为1型HS患者预后良好的原因提供了基础依据。研究设计：本研究采用Illumina HiSeq 2500平台，通过二代测序技术对两组（ILAE 1型HS组、无海马硬化组）各3份海马组织标本的miRNA表达谱进行检测。