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Introduction
Gliomas, originating from neural stem cells, are the predominant and most malignant form of brain cancer in adults [1]. As reported, gliomas account for 24% of all primary brain and CNS tumors and exhibit a wide histological range from benign ependymal tumors to deadly grade IV glioblastoma (GBM) [2, 3–4]. Most patients with untreated gliomas exhibit physical impairments such as fatigue, pain, loss of appetite, insomnia, and nausea/vomiting [5]. Among them, insomnia, defined as difficulty initiating or maintaining sleep, is one of the most common complaints in recurrent glioma patients regardless of grade. A retrospective analysis showed that 46.8% of 340 recurrent glioma patients reported insomnia with a long-term serious impairment of the quality of life in patients [6, 7]. This may be owed to tumor-induced local pressure, activation of the inflammatory response of tumor cells, disturbance of sleep-related neurotransmitters, and changes in various neural circuits in the tumor [8, 9]. However, the relationship between gliomas and insomnia does not appear to be a one-way directed relationship. In recent years, there has been a significant reciprocal relationship between sleep disorders, including insomnia, and tumor. For patients suffering from prostate, breast or colorectal cancer, post-cancer insomnia can develop into a long-term chronic condition that affects their lives more severely than the cancer diagnosis and treatment [10]. At the same time, persistent sleep disturbance heightens the risk of cancer recurrence and death in the patients mentioned above [11, 12–13]. For patients with glioma, the effect of insomnia has not been fully understood. However, research performed by Marthe et al. revealed that 41% of glioma patients had sleep disturbances one year before their glioma diagnosis [14]. Despite the study’s limited sample size. (n = 59), the findings suggested the potential negative impact of insomnia on gliomas.
To understand how insomnia influences glioma patients, it will be critical to explore the molecular mechanisms that may cause this symptom. Sleep behavior is the result of homeostatic drive and circadian rhythms [15]. Among them, the biological circadian rhythm is regulated by specific clock genes in the body. These clock genes, also called circadian rhythm-related genes (CRRGs), play a role in the transcription-translation feedback loop, so that cells and the whole body exhibit certain rhythmic behaviors [16]. Once the expression of these genes...