College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.
J Mol Neurosci. 2021 Oct;71(10):1967-1974. doi: 10.1007/s12031-021-01845-3. Epub 2021 May 16.
In recent years, the incidence of fatigue has been increasing, and the effective prevention and treatment of fatigue has become an urgent problem. As a result, the genetic research of fatigue has become a hot spot. Transcriptome-level regulation is the key link in the gene regulatory network. The transcriptome includes messenger RNAs (mRNAs) and noncoding RNAs (ncRNAs). MRNAs are common research targets in gene expression profiling. Noncoding RNAs, including miRNAs, lncRNAs, circRNAs and so on, have been developed rapidly. Studies have shown that miRNAs are closely related to the occurrence and development of fatigue. MiRNAs can regulate the immune inflammatory reaction in the central nervous system (CNS), regulate the transmission of nerve impulses and gene expression, regulate brain development and brain function, and participate in the occurrence and development of fatigue by regulating mitochondrial function and energy metabolism. LncRNAs can regulate dopaminergic neurons to participate in the occurrence and development of fatigue. This has certain value in the diagnosis of chronic fatigue syndrome (CFS). CircRNAs can participate in the occurrence and development of fatigue by regulating the NF-κB pathway, TNF-α and IL-1β. The ceRNA hypothesis posits that in addition to the function of miRNAs in unidirectional regulation, mRNAs, lncRNAs and circRNAs can regulate gene expression by competitive binding with miRNAs, forming a ceRNA regulatory network with miRNAs. Therefore, we suggest that the miRNA-centered ceRNA regulatory network is closely related to fatigue. At present, there are few studies on fatigue-related ncRNA genes, and most of these limited studies are on miRNAs in ncRNAs. However, there are a few studies on the relationship between lncRNAs, cirRNAs and fatigue. Less research is available on the pathogenesis of fatigue based on the ceRNA regulatory network. Therefore, exploring the complex mechanism of fatigue based on the ceRNA regulatory network is of great significance. In this review, we summarize the relationship between miRNAs, lncRNAs and circRNAs in ncRNAs and fatigue, and focus on exploring the regulatory role of the miRNA-centered ceRNA regulatory network in the occurrence and development of fatigue, in order to gain a comprehensive, in-depth and new understanding of the essence of the fatigue gene regulatory network.
近年来，疲劳的发病率不断上升，有效预防和治疗疲劳已成为当务之急。因此，疲劳的遗传研究成为热点。转录组水平调节是基因调控网络中的关键环节。转录组包括信使 RNA（mRNA）和非编码 RNA（ncRNA）。mRNA 是基因表达谱研究的常见靶点。非编码 RNA 包括 miRNA、lncRNA、circRNA 等，发展迅速。研究表明，miRNA 与疲劳的发生发展密切相关。miRNA 可以调节中枢神经系统（CNS）中的免疫炎症反应，调节神经冲动的传递和基因表达，调节脑发育和脑功能，通过调节线粒体功能和能量代谢参与疲劳的发生发展。lncRNA 可以调节多巴胺能神经元参与疲劳的发生发展。这在慢性疲劳综合征（CFS）的诊断中具有一定价值。circRNA 可以通过调节 NF-κB 通路、TNF-α 和 IL-1β 参与疲劳的发生发展。ceRNA 假说认为，除了 miRNA 单向调节的功能外，mRNA、lncRNA 和 circRNA 还可以通过与 miRNA 竞争性结合来调节基因表达，形成 miRNA 为中心的 ceRNA 调控网络。因此，我们认为以 miRNA 为中心的 ceRNA 调控网络与疲劳密切相关。目前，关于疲劳相关 ncRNA 基因的研究较少，这些有限的研究大多集中在 ncRNA 中的 miRNA 上。然而，关于 lncRNA、cirRNA 与疲劳的关系的研究较少。基于 ceRNA 调控网络的疲劳发病机制的研究较少。因此，基于 ceRNA 调控网络探索疲劳的复杂机制具有重要意义。在这篇综述中，我们总结了 ncRNA 中 miRNA、lncRNA 和 circRNA 与疲劳的关系，并重点探讨了以 miRNA 为中心的 ceRNA 调控网络在疲劳发生发展中的调节作用，以期对疲劳基因调控网络的本质有一个全面、深入和新的认识。
