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人类颞叶癫痫伴海马硬化 ILAE 1 型的环状 RNA 和 mRNA 分析谱

Profiling Analysis of Circular RNA and mRNA in Human Temporal Lobe Epilepsy with Hippocampal Sclerosis ILAE Type 1.

机构信息

Department of Neurosurgery, The First Affiliated Hospital, Harbin Medical University, Harbin, 150001, Heilongjiang, China.

Department of Pathology, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, China.

出版信息

Cell Mol Neurobiol. 2022 Nov;42(8):2745-2755. doi: 10.1007/s10571-021-01136-w. Epub 2021 Aug 2.

Abstract

Hippocampal sclerosis (HS) is the most common surgical pathology associated with temporal lobe epilepsy (TLE). However, the cause of TLE with or without HS remains unknown. Our current study aimed to illustrate the essential molecular mechanism that is potentially involved in the pathogenesis of TLE-HS and to shed light on the transcriptional changes associated with hippocampal sclerosis. Compared to no-HS group, 341 mRNA transcripts and 131 circRNA transcripts were differentially expressed in ILAE type 1 group. The raw sequencing data have been deposited into sequence-read archive (SRA) database under accession number PRJNA699348.Gene Ontology analysis demonstrated that the dysregulated genes were associated with the biological processes of vesicle-mediated transport. Enrichment analysis demonstrated that dysregulated genes were involved mainly in the MAPK signal pathway. Subsequently, A total of 441 known or predicted interactions were formed among DEGs, and the most important module was detected in the PPI network using the MCODE plug-in. There were mainly four functional modules enriched: ER to Golgi transport vesicle membrane, Basal transcription factors, GABA-gated chloride ion channel activity, CENP-A containing nucleosome assembly. A circRNA-mRNA co-expression network was constructed including 5 circRNAs(hsa_circ_0025349, hsa_circ_0002405, hsa_circ_0004805, hsa_circ_0032254, and hsa_circ_0032875) and three mRNAs (FYN, SELENBP1, and GRIPAP1) based on the normalized mRNA signal intensities. This is the first to report the circRNAs and mRNAs expression profile of surgically resected hippocampal tissues from TLE patients of ILAE-1 and no-HS, and these results may provide new insight into the transcriptional changes associated with this pathology.

摘要

海马硬化(HS)是与颞叶癫痫(TLE)相关的最常见的手术病理学。然而,伴有或不伴有 HS 的 TLE 的病因仍然未知。我们目前的研究旨在阐明可能与 TLE-HS 发病机制相关的基本分子机制,并阐明与海马硬化相关的转录变化。与无 HS 组相比,1 型 ILAE 组有 341 个 mRNA 转录本和 131 个 circRNA 转录本差异表达。原始测序数据已被存入 SRA 数据库,注册号为 PRJNA699348。GO 分析表明,失调基因与囊泡介导的运输的生物学过程有关。富集分析表明,失调基因主要参与 MAPK 信号通路。随后,在 DEGs 之间总共形成了 441 个已知或预测的相互作用,并且使用 MCODE 插件在 PPI 网络中检测到最重要的模块。在功能模块富集分析中主要发现了四个功能模块:内质网到高尔基体运输囊泡膜、基础转录因子、GABA 门控氯离子通道活性、含 CENP-A 的核小体组装。基于标准化的 mRNA 信号强度,构建了一个包括 5 个 circRNA(hsa_circ_0025349、hsa_circ_0002405、hsa_circ_0004805、hsa_circ_0032254 和 hsa_circ_0032875)和 3 个 mRNA(FYN、SELENBP1 和 GRIPAP1)的 circRNA-mRNA 共表达网络。这是首次报道 ILAE-1 和无 HS 的 TLE 患者手术切除海马组织的 circRNAs 和 mRNAs 表达谱,这些结果可能为与该病理学相关的转录变化提供新的见解。

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