Department of Neurology, Zhejiang Hospital, Hangzhou, 310000, Zhejiang, China.
Interdiscip Sci. 2019 Dec;11(4):645-654. doi: 10.1007/s12539-019-00319-w. Epub 2019 Feb 4.
Alzheimer's disease (AD) is one of the most common types of dementia among the elderly. Previous studies had revealed that the dysregulation of lncRNAs played important roles in human diseases, including AD. However, there is still a lack of comprehensive analysis of differently expressed long non-coding RNAs (lncRNAs) in different distinct regions related to AD. In present study, we identified a total of 678, 593, 941, 1445, 1179, 466 differently expressed lncRNAs that were found in entorhinal cortex (EC), middle temporal gyrus(MTG), hippocampus (HIP), superior frontal gyrus (SFG), posterior cingulate (PC), cortex and primary visual cortex (VCX) AD samples, respectively. Furthermore, we constructed lncRNA-mRNA co-expression networks in AD to explore the potential roles of these lncRNAs. Differentially expressed (DE) lncRNAs were involved in regulating metabolic process, respiratory electron transport chain and ATP metabolic process showed by GO analysis. Interestingly, KEGG analysis revealed these lncRNAs were associated with neurodegenerative disorders such as Alzheimer's disease, Huntington's disease and Parkinson's disease. Four lncRNAs (LOC100507557, LOC101929787, NEAT1, and JAZF1-AS1) were identified as key lncRNAs in AD progression and dysregulated in different distinct regions related to AD. Our study has uncovered several key lncRNAs in AD, which would give novel underlying therapeutic and prognostic targets for AD.
阿尔茨海默病(AD)是老年人中最常见的痴呆症类型之一。先前的研究表明,lncRNAs 的失调在包括 AD 在内的人类疾病中发挥着重要作用。然而,目前仍然缺乏对 AD 相关不同区域差异表达的长非编码 RNA(lncRNA)的全面分析。在本研究中,我们分别在内嗅皮层(EC)、颞中回(MTG)、海马体(HIP)、额上回(SFG)、后扣带回(PC)、大脑皮质和初级视觉皮层(VCX)AD 样本中鉴定出了总共 678、593、941、1445、1179、466 个差异表达的 lncRNA。此外,我们构建了 AD 中的 lncRNA-mRNA 共表达网络,以探讨这些 lncRNA 的潜在作用。GO 分析显示,差异表达(DE)lncRNA 参与调节代谢过程、呼吸电子传递链和 ATP 代谢过程。有趣的是,KEGG 分析显示这些 lncRNA 与神经退行性疾病如阿尔茨海默病、亨廷顿病和帕金森病有关。四个 lncRNA(LOC100507557、LOC101929787、NEAT1 和 JAZF1-AS1)被鉴定为 AD 进展中的关键 lncRNA,并在 AD 相关不同区域中失调。我们的研究揭示了 AD 中的几个关键 lncRNA,为 AD 提供了新的潜在治疗和预后靶点。