Yu Shengkun, Gu Yifei, Wang Tianyu, Mu Long, Wang Haiyang, Yan Shi, Wang Aoweng, Wang Jiabin, Liu Li, Shen Hong, Na Meng, Lin Zhiguo
Department of Neurosurgery, The First Affiliated Hospital, Harbin Medical University, Harbin, China.
Front Neurosci. 2021 Nov 12;15:770627. doi: 10.3389/fnins.2021.770627. eCollection 2021.
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 (), 7 DEmiRNAs (), and 3 DEmRNAs (), 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)是难治性颞叶癫痫(TLE)最常见的病理类型之一,其特征通常为海马萎缩、神经元凋亡和神经胶质增生。然而,HS患者神经元凋亡的分子机制仍未完全阐明。因此,我们开展了一项初步研究,聚焦于难治性TLE患者硬化海马中的神经元凋亡ceRNA网络。在本研究中,利用RNA测序(RNA-seq)对伴有HS的TLE患者(HS-TLE)和不伴有HS的TLE患者(非HS-TLE)lncRNAs、miRNAs和mRNAs的表达水平进行定量,并采用逆转录定量PCR(qRT-PCR)。通过StarBase v3.0整合差异表达(DE)lncRNAs-miRNAs或DE miRNAs-mRNAs之间的相互作用,并使用Cytoscape进行可视化。随后,我们通过分析lncRNA相关竞争性内源RNA(ceRNA)网络与mRNAs的相互作用来注释其功能。RNA-seq分析显示,与非HS-TLE相比,HS-TLE中有381个lncRNAs、42个miRNAs和457个mRNAs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DE lncRNAs、7个DE miRNAs和3个DE mRNAs组成,它们属于凋亡和癫痫相关条目。我们的研究结果基于转录组测序建立了首个HS-TLE中lncRNA介导的神经元凋亡ceRNA网络,为HS的疾病发病机制和精准治疗提供了新的视角。