Data_Sheet_1_Study of Neuronal Apoptosis ceRNA Network in Hippocampal Sclerosis of Human Temporal Lobe Epilepsy by RNA-Seq.pdf

Hippocampal sclerosis (HS) is one of the most common pathological type of intractable temporal lobe epilepsy (TLE), often characterized by hippocampal atrophy, neuronal apoptosis, and gliogenesis. However, the molecular mechanisms of neuronal apoptosis in patients with HS are still not fully understood. We therefore conducted a pilot study focusing on the neuronal apoptosis ceRNA network in the sclerotic hippocampus of intractable TLE patients. In this research, RNA sequencing (RNA-seq) was utilized to quantify the expression levels of lncRNAs, miRNAs, and mRNAs in TLE patients with HS (HS-TLE) and without HS (non-HS-TLE), and reverse transcription-quantitative PCR (qRT-PCR). The interactions of differential expression (DE) lncRNAs-miRNAs or DEmiRNAs-mRNAs were integrated by StarBase v3.0, and visualized using Cytoscape. Subsequently, we annotate the functions of lncRNA-associated competitive endogenous RNA (ceRNA) network through analysis of their interactions with mRNAs. RNA-seq analyses showed 381 lncRNAs, 42 miRNAs, and 457 mRNAs were dysregulated expression in HS-TLE compared to non-HS-TLE. According to the ceRNA hypothesis, 5 HS-specific ceRNA network were constructed. Among them, the core ceRNA regulatory network involved in neuronal apoptosis was constituted by 10 DElncRNAs (CDKN2B-AS1, MEG3, UBA6-AS1, etc.), 7 DEmiRNAs (hsa-miR-155-5p, hsa-miR-195-5p, hsa-miR-200c-3p, etc.), and 3 DEmRNAs (SCN2A, DYRK2, and MAPK8), which belonging to apoptotic and epileptic terms. Our findings established the first ceRNA network of lncRNA-mediated neuronal apoptosis in HS-TLE based on transcriptome sequencing, which provide a new perspective on the disease pathogenesis and precise treatments of HS.

海马硬化（HS）是难以治疗的颞叶癫痫（TLE）中最常见的病理类型之一，通常以海马萎缩、神经元凋亡和胶质生成为特征。然而，海马硬化患者神经元凋亡的分子机制仍尚未完全明了。因此，我们开展了一项以难以治疗的TLE患者硬化海马中的神经元凋亡竞争性内源RNA（ceRNA）网络为研究重点的试点研究。在本研究中，利用RNA测序（RNA-seq）对TLE患者中具有HS（HS-TLE）和不具有HS（非HS-TLE）的海马硬化患者的长链非编码RNA（lncRNA）、微小RNA（miRNA）和信使RNA（mRNA）的表达水平进行量化，并采用逆转录定量PCR（qRT-PCR）。通过StarBase v3.0整合差异表达（DE）lncRNA-miRNA或DEmiRNA-mRNA的相互作用，并使用Cytoscape进行可视化。随后，通过分析其与mRNA的相互作用来注释lncRNA相关ceRNA网络的功能。RNA-seq分析显示，与无HS-TLE相比，HS-TLE中失调表达的lncRNA有381个，miRNA有42个，mRNA有457个。根据ceRNA假说，构建了5个HS特异性ceRNA网络。其中，涉及神经元凋亡的核心ceRNA调控网络由10个DElncRNA（CDKN2B-AS1、MEG3、UBA6-AS1等）、7个DEmiRNA（hsa-miR-155-5p、hsa-miR-195-5p、hsa-miR-200c-3p等）和3个DEmRNA（SCN2A、DYRK2、MAPK8）构成，这些均属于凋亡和癫痫相关术语。我们的研究结果基于转录组测序，建立了HS-TLE中lncRNA介导的神经元凋亡的第一ceRNA网络，为HS的疾病发病机制和精准治疗提供了新的视角。