Genome‐scale biological studies conducted in the post‐genomic era have revealed that two‐thirds of human genes do not encode proteins. Most functional non‐coding RNA transcripts in humans are products of long non‐coding RNA (lncRNA) genes, an abundant but still poorly understood class of human genes. As a result of their fundamental and multitasking regulatory roles, lncRNAs are associated with a wide range of human diseases, including neurological disorders. Approximately 40% of lncRNAs are specifically expressed in the brain, and many of them exhibit distinct spatiotemporal patterns of expression. Comparative genomics approaches have determined that 65%–75% of human lncRNA genes are primate‐specific and hence can be posited as a contributing potential cause of the higher‐order complexity of primates, including human, brains relative to those of other mammals. Although lncRNAs present important mechanistic examples of epileptogenic functions, the human/primate specificity of lncRNAs questions their relevance in rodent models. Here, we present an in‐depth review that supports the contention that human lncRNAs are direct contributors to the etiology and pathogenesis of human epilepsy, as a means to accelerate the integration of lncRNAs into clinical practice as potential diagnostic biomarkers and therapeutic targets. Meta‐analytically, the major finding of our review is the commonality of lncRNAs in epilepsy and cancer pathogenesis through mitogen‐activated protein kinase (MAPK)‐related pathways. In addition, neuroinflammation may be a relevant part of the common pathophysiology of cancer and epilepsy. LncRNAs affect neuroinflammation‐related signaling pathways such as nuclear factor kappa‐ light‐ chain‐ enhancer of activated B cells (NF‐κB), Notch, and phosphatidylinositol 3‐ kinase/ protein kinase B (Akt) (PI3K/AKT), with the NF‐κB pathway being the most common. Besides the controversy over lncRNA research in non‐primate models, whether neuroinflammation is triggered by injury and/or central nervous system (CNS) toxicity during epilepsy modeling in animals or is a direct consequence of epilepsy pathophysiology needs to be considered meticulously in future studies.

中文翻译：

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长链非编码 RNA 在人类癫痫中的新作用

后基因组时代进行的基因组规模的生物学研究表明，三分之二的人类基因不编码蛋白质。人类中大多数功能性非编码 RNA 转录物都是长非编码 RNA (lncRNA) 基因的产物，这是一类丰富但仍知之甚少的人类基因。由于其基本和多任务调节作用，lncRNA 与多种人类疾病相关，包括神经系统疾病。大约 40% 的 lncRNA 在大脑中特异性表达，其中许多表现出独特的时空表达模式。比较基因组学方法已经确定，65%–75% 的人类 lncRNA 基因是灵长类动物特异性的，因此可以被认为是灵长类动物（包括人类）大脑相对于其他哺乳动物的大脑具有高阶复杂性的潜在原因。尽管lncRNA提供了致癫痫功能的重要机制实例，但lncRNA的人类/灵长类特异性质疑它们在啮齿动物模型中的相关性。在这里，我们提出了一篇深入的综述，支持人类lncRNA是人类癫痫病因和发病机制的直接贡献者的论点，作为加速lncRNA作为潜在诊断生物标志物和治疗靶点融入临床实践的一种手段。荟萃分析表明，我们综述的主要发现是 lncRNA 通过丝裂原激活蛋白激酶 (MAPK) 相关途径在癫痫和癌症发病机制中的共性。此外，神经炎症可能是癌症和癫痫常见病理生理学的相关部分。 LncRNA 影响神经炎症相关信号通路，例如活化 B 细胞的核因子 kappa 轻链增强子 (NF-κB)、Notch 和磷脂酰肌醇 3 激酶/蛋白激酶 B (Akt) (PI3K/AKT)， NF-κB 通路是最常见的。除了非灵长类动物模型中 lncRNA 研究的争议之外​​，神经炎症是否是由动物癫痫建模过程中的损伤和/或中枢神经系统（CNS）毒性引发的，还是癫痫病理生理学的直接后果，需要在未来的研究中仔细考虑。