• Wenwen Zhu, Xingchun Yang, Nanxi Li, Bin Zhang, Lishan Huang, Hanxing Cheng, Xiao Wu, Dechou Zhang, Sen Li, and Houping Xu.
• Geriatric Department, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China.
• Medicine (Baltimore). 2025 Jan 17; 104 (3): e40965e40965.

AbstractInsomnia is increasingly common and poses significant health risks. The aims of this study are to identify apoptosis-related genes and potential biomarkers for insomnia and to find new therapeutic targets. Insomnia gene expression profiles were downloaded from the Gene Expression Omnibus database, and differentially expressed genes in normal and insomnia samples were identified by limma rapid differential analysis, and then the major modular genes with clinical relevance to insomnia were analyzed using the Weighted Gene Co-Expression Network Analysis, and intersections were obtained with the differentially expressed genes as well as with apoptotic gene databases. We validated apoptosis-related differentially expressed genes, enriched and analyzed the specific biological process of insomnia and related signaling pathways. In addition, we constructed a protein-protein interaction network and obtained Top10 hub genes using Cytoscape. We selected 3 of them as hub genes and compared their expression in normal hippocampal neuronal cells and hippocampal neuronal cells of the model group exposed to corticosterone induction by Western Blot and qRT-PCR experiments. A total of 190 differentially expressed apoptosis-related genes were identified in insomnia, and BCL2, SOCS3, and IL7R were identified as important hub genes. Enrichment analysis showed that the occurrence of apoptosis in insomnia was mainly related to "PI3K-Akt signaling pathway," "JAK-STAT signaling pathway," "P53 signaling pathway" and so on. GO analysis showed that apoptosis in insomnia was mainly related to "immune response," "T cell differentiation in thymus," and "positive regulation of MAPK cascade." Western Blot and qRT-PCR experiments showed that BCL2, SOCS3, IL7R antiapoptotic indexes were under-expressed in modeled hippocampal neuronal cells compared to normal hippocampal neuronal cells. This study emphasizes the role of apoptosis-related genes in insomnia and preliminarily predicts that the occurrence of insomnia is closely related to apoptosis. Compared to the normal group, the antiapoptotic ability of hippocampal neurons in the model group is reduced. Although BCL2 has been studied in the context of sleep deprivation, SOCS3 and IL7R have not yet been explored in insomnia. Insomnia and sleep deprivation involve similar pathways, but due to different mechanisms and types of insomnia, gene expression may vary.Copyright © 2025 the Author(s). Published by Wolters Kluwer Health, Inc.

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