与人类内侧颞叶癫痫中海马硬化相关的差异长链非编码RNA（lncRNA）图谱。
Differential long non-coding RNA (lncRNA) profiles associated with hippocampal sclerosis in human mesial temporal lobe epilepsy.
作者信息
Cui Zhiqiang, Zhang Xiufeng, Song Huifang, Yang Fuxing, Feng Shiyu, Feng Lin, Ling Zhipei, Pan Longsheng, Liang Shuli, Mao Zhiqi, Bu Bo, Chen Lifeng, Yu Xinguang, Xu Bainan
机构信息
Department of Neurosurgery, Chinese PLA General Hospital, Chinese PLA Postgraduate Medical School Beijing 100853, China.
Department of Neurosurgery, Affiliated Tangshan People's Hospital and Tangshan Cancer Hospital North China University of Science and Technology Tangshan 063000, China.
出版信息
Int J Clin Exp Pathol. 2019 Jan 1;12(1):259-266. eCollection 2019.
OBJECTIVE
The aim of this study was to analyze the expression profiles of long non-coding RNA (lncRNAs) in human mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS) and to detect the functions of lncRNAs in epileptogenesis in MTLE.
MATERIALS AND METHODS
We used microarray analysis to analyze the differential expression of lncRNAs and mRNAs in three hippocampal sclerosis and three normal hippocampus samples. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the microarrray results. A coding and non-coding gene co-expression network was constructed based on the correlation between the differential expression of lncRNAs and mRNAs. Gene ontology (GO) and pathway analyses were then performed to determine the potential roles of the differentially expressed mRNAs in the co-expression network. Lastly, to understand potential functions of lncRNAs in MTLE, cis-/trans-acting lncRNAs were predicted using bioinformatic analysis.
RESULTS
Compared with control hippocampus, 497 differentially expressed lncRNAs were identified in the hippocampal sclerosis samples, consisting of 294 up-regulated and 203 down-regulated lncRNAs (fold-change >2.0 or <-2.0, P<0.05). Similarly, 399 differentially expressed mRNAs were identified with 236 up-regulated and 163 down-regulated. There were 356 lncRNAs and 332 mRNAs in the non-coding and coding co-expression network, in which the highly enriched GO categories were related to the inflammatory response, and neuropeptide receptor activity. Nine pairs of lncRNAs and mRNAs (located within 10 kb of each other) were found to exert functional effects on epileptogenesis.
CONCLUSION
Differential expression of lncRNAs of varying length and location were observed in human MTLE with hippocampal sclerosis. The dysregulated lncRNAs with co-dysregulated mRNAs in inflammatory response and neuropeptide receptor activity categories are predicted to play roles in epileptogenesis in MTLE. LncRNA may contribute to epileptogenesis by targeting .
目的
本研究旨在分析伴有海马硬化（HS）的人类内侧颞叶癫痫（MTLE）中长链非编码RNA（lncRNAs）的表达谱，并检测lncRNAs在MTLE癫痫发生中的作用。
材料与方法
我们使用微阵列分析来分析三个海马硬化样本和三个正常海马样本中lncRNAs和mRNAs的差异表达。采用定量实时聚合酶链反应（qRT-PCR）验证微阵列结果。基于lncRNAs和mRNAs差异表达之间的相关性构建编码和非编码基因共表达网络。然后进行基因本体（GO）和通路分析，以确定共表达网络中差异表达的mRNAs的潜在作用。最后，为了解lncRNAs在MTLE中的潜在功能，使用生物信息学分析预测顺式/反式作用lncRNAs。
结果
与对照海马相比，在海马硬化样本中鉴定出497个差异表达的lncRNAs，其中294个上调，203个下调（倍数变化>2.0或<-2.0，P<0.05）。同样，鉴定出399个差异表达的mRNAs，其中236个上调，163个下调。在非编码和编码共表达网络中有356个lncRNAs和332个mRNAs，其中高度富集的GO类别与炎症反应和神经肽受体活性有关。发现九对lncRNAs和mRNAs（彼此位于10 kb内）对癫痫发生有功能影响。
结论
在伴有海马硬化的人类MTLE中观察到不同长度和位置的lncRNAs的差异表达。预测在炎症反应和神经肽受体活性类别中与失调的mRNAs共失调的lncRNAs在MTLE的癫痫发生中起作用。LncRNA可能通过靶向 促进癫痫发生。
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