Tan Liucen, Zhao Wenfeng, Wang Huang, Huang Xinqi, Li Rui, Yin Lin, Liu Xiaolei, Wang Junhui, Wu Nan, Wang Hongxing
Division of Neuropsychiatry and Psychosomatics, Department of Neurology, Xuanwu Hospital, National Center for Neurological Disorders, National Clinical Research Center for Geriatric Diseases, Capital Medical University, Beijing, China.
Department of Neurology, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
Mol Psychiatry. 2025 Aug 22. doi: 10.1038/s41380-025-03167-x.
Circular RNAs (circRNAs), characterized by their unique covalently closed circular structure, are highly stable, conserved, and expressed in a tissue-, cell-, and developmental stage-specific manner. A lot of evidence has indicated that circRNAs play a crucial role in diversified biological and pathological processes by sponging microRNAs (miRNAs), interacting with proteins, or being translated into particular proteins, etc. Recent advancements in bioinformatics have revealed a close association between circRNAs and the development of neuropsychiatric diseases, including major depressive disorder (MDD). Increasingly, researchers emphasize the significant impact of abnormal circRNA expression and its targets on the pathogenesis of MDD. However, the detailed mechanisms involved remain elusive. Research has articulated the important role of neuronal cell dysfunction in MDD. Glia cells are the most abundant cell type in the central nervous system (CNS) and provide critical roles in MDD via intercellular-interaction-dependent pathogenic mechanisms. In this review, we extensively explore the newly identified roles of circRNAs in MDD. We summarize their novel mechanisms from cellular and molecular perspectives by deciphering how circRNAs interplay between neurons and neurogliocytes, followed by how circRNAs are tailored to synaptic plasticity and stress pathways under a variety of circumstances. Last, we discuss and predict their potential clinical values of diagnosis and therapy.
环状RNA（circRNAs）具有独特的共价闭合环状结构，高度稳定、保守，并以组织、细胞和发育阶段特异性的方式表达。大量证据表明，circRNAs通过充当微小RNA（miRNAs）的海绵、与蛋白质相互作用或被翻译成特定蛋白质等方式，在多种生物学和病理过程中发挥关键作用。生物信息学的最新进展揭示了circRNAs与神经精神疾病（包括重度抑郁症，MDD）发生发展之间的密切关联。越来越多的研究人员强调circRNA异常表达及其靶点对MDD发病机制的重大影响。然而，其中涉及的详细机制仍不清楚。研究表明神经元细胞功能障碍在MDD中起重要作用。神经胶质细胞是中枢神经系统（CNS）中最丰富的细胞类型，通过细胞间相互作用依赖的致病机制在MDD中发挥关键作用。在本综述中，我们广泛探讨了circRNAs在MDD中最新发现的作用。我们从细胞和分子角度总结了它们的新机制，解读了circRNAs如何在神经元和神经胶质细胞之间相互作用，以及在各种情况下circRNAs如何调节突触可塑性和应激途径。最后，我们讨论并预测了它们在诊断和治疗方面的潜在临床价值。
