Accumulating evidence has highlighted the important roles of long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) in Alzheimer's disease (AD). In this study, we constructed an AD-derived lncRNA-associated ceRNA network (LncACeNET) based on the ceRNA hypothesis and co-expressed correlation analysis of RNAs (miRNAs, mRNAs and lncRNAs) from AD patients. Based on this network, we preliminarily identified new potential AD biomarkers including hsa-miR-155-5p, CERS6-AS1, and CTB-89H12.4. The functional enrichment analysis demonstrated that these inferred biomarkers were significantly correlated with AD-related biological processes such as neuron projection development and neuron projection morphogenesis. Notably, lncRNA CTB-89H12.4 is significantly associated with “calcium ion-regulated exocytosis of neurotransmitter”, “chemical synaptic transmission”, “presynaptic membrane assembly”, “receptor localization to synapse”, and “learning”. This indicates the important role of CTB-89H12.4 as a promising target for AD therapy. Subsequently, we used the computational pipeline DTINet and discovered 19 lines of probable therapeutic relationships between FDA-approved drugs and CTB-89H12.4, which offered a new avenue to repurpose existing FDA-approved drugs for AD indication. Our study provides a new landscape for LncACeNET in AD, and will benefit mechanism study and new drug development for AD.

中文翻译：

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对与lncRNA相关的ceRNA网络的综合分析可确定阿尔茨海默氏病的神经炎症生物标记物。

越来越多的证据突出了长非编码RNA（lncRNA）在阿尔茨海默氏病（AD）中作为竞争性内源RNA（ceRNA）的重要作用。在这项研究中，我们基于ceRNA假设和共表达来自AD患者的RNA（miRNA，mRNA和lncRNA）的相关分析，构建了与AD衍生的lncRNA相关的ceRNA网络（LncACeNET）。基于该网络，我们初步鉴定了新的潜在AD生物标记，包括hsa-miR-155-5p，CERS6-AS1和CTB-89H12.4。功能富集分析表明，这些推断的生物标志物与AD相关的生物学过程（如神经元投射发育和神经元投射形态发生）显着相关。值得注意的是，lncRNA CTB-89H12.4与“钙离子调节的神经递质的胞吐作用”显着相关，“化学突触传递”，“突触前膜组装”，“受体定位于突触”和“学习”。这表明CTB-89H12.4作为AD治疗的有希望的靶标具有重要作用。随后，我们使用了计算管道DTINet，发现了FDA批准的药物与CTB-89H12.4之间可能存在的19种治疗关系，这为将现有FDA批准的药物用于AD适应症提供了新途径。我们的研究为LncACeNET在AD中提供了新的前景，并将有益于AD的机理研究和新药开发。我们使用了DTINet计算管道，并发现了FDA批准的药物与CTB-89H12.4之间可能存在的19种治疗关系，这为将现有FDA批准的药物用于AD适应症提供了新途径。我们的研究为LncACeNET在AD中提供了新的前景，并将有益于AD的机理研究和新药开发。我们使用了DTINet计算管道，并发现了FDA批准的药物与CTB-89H12.4之间可能存在的19种治疗关系，这为将现有FDA批准的药物用于AD适应症提供了新途径。我们的研究为LncACeNET在AD中提供了新的前景，并将有益于AD的机理研究和新药开发。