PDF(Pubmed)
Abstract：
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.
摘要：
海马硬化(HS)是顽固性颞叶癫痫(TLE)最常见的病理类型,通常以海马萎缩为特征，神经元凋亡，和神经胶质生成。然而,HS患者神经细胞凋亡的分子机制尚不完全清楚。因此，我们进行了一项针对难治性TLE患者硬化海马中神经元凋亡ceRNA网络的初步研究。在这项研究中,RNA测序（RNA-seq）用于定量lncRNAs的表达水平，miRNA,和有HS（HS-TLE）和无HS（非HS-TLE）的TLE患者的mRNA，和逆转录-定量PCR(qRT-PCR)。通过StarBasev3.0整合差异表达（DE）lncRNAs-miRNAs或DEmiRNAs-mRNAs的相互作用，并使用Cytoscape进行可视化。随后，我们通过分析lncRNA与mRNA的相互作用来注释lncRNA相关的竞争性内源性RNA（ceRNA）网络的功能。RNA-seq分析显示381个lncRNAs，42个miRNA,与非HS-TLE相比，HS-TLE中的457个mRNA表达失调。根据ceRNA假说,构建了5个HS特异性ceRNA网络。其中,参与神经元凋亡的核心ceRNA调控网络由10个DElncRNA(CDKN2B-AS1、MEG3、UBA6-AS1等)构成。),7个DEmiRNA（hsa-miR-155-5p，hsa-miR-195-5p,hsa-miR-200c-3p,等。),和3个DEmRNAs(SCN2A，DYRK2和MAPK8），属于凋亡性和癫痫性术语。我们的发现基于转录组测序建立了lncRNA介导的HS-TLE神经元凋亡的第一个ceRNA网络，为HS的发病机制和精准治疗提供了新的视角。
