Zhang Lin-Ming, Chen Ling, Zhao Yi-Fei, Duan Wei-Mei, Zhong Lian-Mei, Liu Ming-Wei
Department of Neurology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
Yunnan Provincial Clinical Research Center for Neurological Disease, Kunming, Yunnan, China.
Front Neurol. 2023 Jul 7;14:1175007. doi: 10.3389/fneur.2023.1175007. eCollection 2023.
One of the most prevalent types of epilepsy is temporal lobe epilepsy (TLE), which has unknown etiological factors and drug resistance. The detailed mechanisms underlying potassium channels in human TLE have not yet been elucidated. Hence, this study aimed to mine potassium channel genes linked to TLE using a bioinformatic approach. The results found that Four key TLE-related potassium channel genes (TERKPCGs) were identified: potassium voltage-gated channel subfamily E member () 1, , potassium inwardly rectifying channel, subfamily J, member 11 (), and . A protein-protein interaction (PPI) network was constructed to analyze the relationship between TERKPCGs and other key module genes. The results of gene set enrichment analysis (GSEA) for a single gene indicated that the four TERKPCGs were highly linked to the cation channel, potassium channel, respiratory chain, and oxidative phosphorylation. The mRNA-TF network was established using four mRNAs and 113 predicted transcription factors. A ceRNA network containing seven miRNAs, two mRNAs, and 244 lncRNAs was constructed based on the TERKPCGs. Three common small-molecule drugs (enflurane, promethazine, and miconazole) target , and . Ten small-molecule drugs (glimepiride, diazoxide, levosimendan, and thiamylal et al.) were retrieved for . Compared to normal mice, the expression of , , , and was downregulated in the brain tissue of the epilepsy mouse model at both the transcriptional and translational levels, which was consistent with the trend of human data from the public database. The results indicated that key potassium channel genes linked to TLE were identified based on bioinformatics analysis to investigate the potential significance of potassium channel genes in the development and treatment of TLE.
最常见的癫痫类型之一是颞叶癫痫(TLE),其病因不明且具有耐药性。人类TLE中钾通道的详细机制尚未阐明。因此,本研究旨在采用生物信息学方法挖掘与TLE相关的钾通道基因。结果发现,鉴定出四个关键的TLE相关钾通道基因(TERKPCGs):钾电压门控通道亚家族E成员1(KCNE1)、内向整流钾通道亚家族J成员11(KCNJ11)等。构建了蛋白质-蛋白质相互作用(PPI)网络以分析TERKPCGs与其他关键模块基因之间的关系。单基因的基因集富集分析(GSEA)结果表明,这四个TERKPCGs与阳离子通道、钾通道、呼吸链和氧化磷酸化高度相关。使用四个mRNA和113个预测的转录因子建立了mRNA-TF网络。基于TERKPCGs构建了一个包含七个miRNA、两个mRNA和244个lncRNA的ceRNA网络。三种常见的小分子药物(恩氟烷、异丙嗪和咪康唑)作用于KCNE1、KCNJ11等。检索到十种针对KCNQ2的小分子药物(格列美脲、二氮嗪、左西孟旦和硫喷妥钠等)。与正常小鼠相比,癫痫小鼠模型脑组织中KCNE1、KCNJ11、KCNQ2和KCNH2的表达在转录和翻译水平均下调,这与公共数据库中的人类数据趋势一致。结果表明,基于生物信息学分析鉴定出了与TLE相关的关键钾通道基因,以研究钾通道基因在TLE发生发展和治疗中的潜在意义。