Jet lag-induced circadian disruption elevates glioma risk by altering molecular profiles in distinct brain regions
Abstract Purpose To investigate the mechanism underlying chronic jet lag (CJL)-induced circadian disruption stimulating glioma-related gene expression across distinct brain regions, and to examine the regulatory role of core clock genes in modulating neural oncogenic susceptibility. Methods This exp...
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| Format: | Article |
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Springer
2025-07-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-025-03253-0 |
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| author | Yong Zhang Wanling Zheng Rufei Dai Tianyi Ma Zonghan Li Jicheng Li Jiawei Shen |
| author_facet | Yong Zhang Wanling Zheng Rufei Dai Tianyi Ma Zonghan Li Jicheng Li Jiawei Shen |
| author_sort | Yong Zhang |
| collection | DOAJ |
| description | Abstract Purpose To investigate the mechanism underlying chronic jet lag (CJL)-induced circadian disruption stimulating glioma-related gene expression across distinct brain regions, and to examine the regulatory role of core clock genes in modulating neural oncogenic susceptibility. Methods This experiment was initiated with the establishment of an animal model of CJL (6-h light-cycle advances every 2 days for 10 or 30 days) in wild-type and clock gene-deficient mice (Bmal1 −/− , Per1/2 −/− , and Cry1/2 −/−). Then, tissues harvested from six neural regions (i.e., hippocampus, prefrontal cortex, striatum, hypothalamus, raphe nuclei, and nucleus accumbens) were subjected to tissue-specific qPCR profiling of cancer-related genes (C-MYC, MDM-2, GADD45A, and p53). Additionally, bioinformatics analyses (DAVID, ConsensusPathDB) was employed to identify pathway interactions, with statistical validation using ANOVA and t-tests. Results CJL induced brain region-specific dysregulation of oncogenic pathways, with marked activation of oncogenes (C-MYC↑, and MDM-2↑) in hypothalamic and striatal regions, while suppression of tumor suppressors (GADD45A↓, and p53↓) in hippocampal and cortical regions. Clock gene mutations amplified these effects, particularly in Bmal1 −/− mice, indicating core clock components as critical modulators of neural oncogenesis. Meanwhile, sex-dependent differences emerged in cerebellar tumor suppressor responses to CJL. Besides, pathway analysis revealed circadian-glioma crosstalk through p53-mediated apoptosis and cell cycle regulation. Conclusion Chronic circadian disruption acts as a brain region-specific oncogenic stressor, driving transcriptional reprogramming of cancer pathways in a clock gene-dependent manner. Mechanistically, our study may establish a relationship of circadian dysfunction with glioma risk, underscoring the necessity for sex-stratified chronotherapeutic approaches in neuro-oncology. |
| format | Article |
| id | doaj-art-b8a5fdcee95243088889fab73058bc39 |
| institution | DOAJ |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-b8a5fdcee95243088889fab73058bc392025-08-20T03:05:14ZengSpringerDiscover Oncology2730-60112025-07-0116112110.1007/s12672-025-03253-0Jet lag-induced circadian disruption elevates glioma risk by altering molecular profiles in distinct brain regionsYong Zhang0Wanling Zheng1Rufei Dai2Tianyi Ma3Zonghan Li4Jicheng Li5Jiawei Shen6Department of Neurosurgery, The Second Affiliated Hospital of Xuzhou Medical UniversityDepartment of Dermatology and Cosmetology, Minhang Hospital, Fudan UniversityDepartment of Neurosurgery, The Second Affiliated Hospital of Xuzhou Medical UniversityDepartment of Neurosurgery, The Second Affiliated Hospital of Xuzhou Medical UniversityDepartment of Neurosurgery, The Second Affiliated Hospital of Xuzhou Medical UniversityDepartment of Neurosurgery, The Second Affiliated Hospital of Xuzhou Medical UniversityDepartment of Neurosurgery, The Second Affiliated Hospital of Xuzhou Medical UniversityAbstract Purpose To investigate the mechanism underlying chronic jet lag (CJL)-induced circadian disruption stimulating glioma-related gene expression across distinct brain regions, and to examine the regulatory role of core clock genes in modulating neural oncogenic susceptibility. Methods This experiment was initiated with the establishment of an animal model of CJL (6-h light-cycle advances every 2 days for 10 or 30 days) in wild-type and clock gene-deficient mice (Bmal1 −/− , Per1/2 −/− , and Cry1/2 −/−). Then, tissues harvested from six neural regions (i.e., hippocampus, prefrontal cortex, striatum, hypothalamus, raphe nuclei, and nucleus accumbens) were subjected to tissue-specific qPCR profiling of cancer-related genes (C-MYC, MDM-2, GADD45A, and p53). Additionally, bioinformatics analyses (DAVID, ConsensusPathDB) was employed to identify pathway interactions, with statistical validation using ANOVA and t-tests. Results CJL induced brain region-specific dysregulation of oncogenic pathways, with marked activation of oncogenes (C-MYC↑, and MDM-2↑) in hypothalamic and striatal regions, while suppression of tumor suppressors (GADD45A↓, and p53↓) in hippocampal and cortical regions. Clock gene mutations amplified these effects, particularly in Bmal1 −/− mice, indicating core clock components as critical modulators of neural oncogenesis. Meanwhile, sex-dependent differences emerged in cerebellar tumor suppressor responses to CJL. Besides, pathway analysis revealed circadian-glioma crosstalk through p53-mediated apoptosis and cell cycle regulation. Conclusion Chronic circadian disruption acts as a brain region-specific oncogenic stressor, driving transcriptional reprogramming of cancer pathways in a clock gene-dependent manner. Mechanistically, our study may establish a relationship of circadian dysfunction with glioma risk, underscoring the necessity for sex-stratified chronotherapeutic approaches in neuro-oncology.https://doi.org/10.1007/s12672-025-03253-0Circadian disruptionGene expressionJet lagMolecular profiles in brain regionsGlioma risk |
| spellingShingle | Yong Zhang Wanling Zheng Rufei Dai Tianyi Ma Zonghan Li Jicheng Li Jiawei Shen Jet lag-induced circadian disruption elevates glioma risk by altering molecular profiles in distinct brain regions Discover Oncology Circadian disruption Gene expression Jet lag Molecular profiles in brain regions Glioma risk |
| title | Jet lag-induced circadian disruption elevates glioma risk by altering molecular profiles in distinct brain regions |
| title_full | Jet lag-induced circadian disruption elevates glioma risk by altering molecular profiles in distinct brain regions |
| title_fullStr | Jet lag-induced circadian disruption elevates glioma risk by altering molecular profiles in distinct brain regions |
| title_full_unstemmed | Jet lag-induced circadian disruption elevates glioma risk by altering molecular profiles in distinct brain regions |
| title_short | Jet lag-induced circadian disruption elevates glioma risk by altering molecular profiles in distinct brain regions |
| title_sort | jet lag induced circadian disruption elevates glioma risk by altering molecular profiles in distinct brain regions |
| topic | Circadian disruption Gene expression Jet lag Molecular profiles in brain regions Glioma risk |
| url | https://doi.org/10.1007/s12672-025-03253-0 |
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