海马硬化型颞叶癫痫的表达谱及潜在致病机制的综合分析
Integrated Analysis of Expression Profile and Potential Pathogenic Mechanism of Temporal Lobe Epilepsy With Hippocampal Sclerosis.
作者信息
Wang Zhi-Bin, Qu Jian, Yang Zhuan-Yi, Liu Ding-Yang, Jiang Shi-Long, Zhang Ying, Yang Zhi-Quan, Mao Xiao-Yuan, Liu Zhao-Qian
机构信息
Department of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, and National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
Institute of Clinical Pharmacology, Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Central South University, Changsha, China.
出版信息
Front Neurosci. 2022 Jun 16;16:892022. doi: 10.3389/fnins.2022.892022. eCollection 2022.
OBJECTIVE
To investigate the potential pathogenic mechanism of temporal lobe epilepsy with hippocampal sclerosis (TLE+HS) by analyzing the expression profiles of microRNA/ mRNA/ lncRNA/ DNA methylation in brain tissues.
METHODS
Brain tissues of six patients with TLE+HS and nine of normal temporal or parietal cortices (NTP) of patients undergoing internal decompression for traumatic brain injury (TBI) were collected. The total RNA was dephosphorylated, labeled, and hybridized to the Agilent Human miRNA Microarray, Release 19.0, 8 × 60K. The cDNA was labeled and hybridized to the Agilent LncRNA+mRNA Human Gene Expression Microarray V3.0,4 × 180K. For methylation detection, the DNA was labeled and hybridized to the Illumina 450K Infinium Methylation BeadChip. The raw data was extracted from hybridized images using Agilent Feature Extraction, and quantile normalization was performed using the Agilent GeneSpring. -value < 0.05 and absolute fold change >2 were considered the threshold of differential expression data. Data analyses were performed using R and Bioconductor. BrainSpan database was used to screen for signatures that were not differentially expressed in normal human hippocampus and cortex (data from BrainSpan), but differentially expressed in TLE+HS' hippocampus and NTP' cortex (data from our cohort). The strategy "Guilt by association" was used to predict the prospective roles of each important hub mRNA, miRNA, or lncRNA.
RESULTS
A significantly negative correlation ( < -0.5) was found between 116 pairs of microRNA/mRNA, differentially expressed in six patients with TLE+HS and nine of NTP. We examined this regulation network's intersection with target gene prediction results and built a lncRNA-microRNA-Gene regulatory network with structural, and functional significance. Meanwhile, we found that the disorder of FGFR3, hsa-miR-486-5p, and lnc-KCNH5-1 plays a key vital role in developing TLE+HS.
目的
通过分析脑组织中微小RNA/信使核糖核酸/长链非编码核糖核酸/DNA甲基化的表达谱，探讨海马硬化型颞叶癫痫（TLE+HS）的潜在致病机制。
方法
收集6例TLE+HS患者的脑组织以及9例因创伤性脑损伤（TBI）接受内减压治疗患者的正常颞叶或顶叶皮质（NTP）。将总RNA去磷酸化、标记，并与安捷伦人类miRNA微阵列（版本19.0，8×60K）杂交。将互补DNA标记并与安捷伦lncRNA+mRNA人类基因表达微阵列V3.0（4×180K）杂交。对于甲基化检测，将DNA标记并与Illumina 450K Infinium甲基化芯片杂交。使用安捷伦特征提取软件从杂交图像中提取原始数据，并使用安捷伦基因弹簧软件进行分位数归一化。P值<0.05且绝对倍数变化>2被视为差异表达数据的阈值。使用R和生物导体进行数据分析。利用BrainSpan数据库筛选在正常人类海马体和皮质中无差异表达（来自BrainSpan的数据），但在TLE+HS海马体和NTP皮质中有差异表达（来自我们队列的数据）的特征。采用“关联有罪”策略预测每个重要枢纽信使核糖核酸、微小RNA或长链非编码核糖核酸的潜在作用。
结果
在6例TLE+HS患者和9例NTP中差异表达的116对微小RNA/信使核糖核酸之间发现显著负相关（P<-0.5）。我们检查了该调控网络与靶基因预测结果的交集，并构建了具有结构和功能意义的长链非编码核糖核酸-微小RNA-基因调控网络。同时，我们发现成纤维细胞生长因子受体3（FGFR3）、hsa-miR-486-5p和lnc-KCNH5-1的紊乱在TLE+HS的发生发展中起关键重要作用。
Zotero 插件