DEHP-Induced Glioblastoma in Zebrafish Is Associated with Circadian Dysregulation of PER3
DEHP is a plasticizer that is widely found in our water environment and poses a significant risk to the environment and human health. Long-term exposure to DEHP can cause endocrine disruption and interfere with the organism’s normal functioning. In order to explore the potential effects of DEHP on t...
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MDPI AG
2024-11-01
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| author | Shuhui Men Jiayun Xu Zhanhong Yang Zhenguang Yan |
| author_facet | Shuhui Men Jiayun Xu Zhanhong Yang Zhenguang Yan |
| author_sort | Shuhui Men |
| collection | DOAJ |
| description | DEHP is a plasticizer that is widely found in our water environment and poses a significant risk to the environment and human health. Long-term exposure to DEHP can cause endocrine disruption and interfere with the organism’s normal functioning. In order to explore the potential effects of DEHP on the development of biological brain tissues, this study used bioinformatics analysis to confirm the diagnostic and prognostic value of PER3 in gliomas and further validated the neurotoxicity of DEHP using methods such as behavioral experiments and molecular biology in zebrafish. The experimental findings revealed that the expression level of PER3 in diseased tissues was significantly lower than that in the control group. In addition, the expression level of PER3 was significantly correlated with immune cell infiltration, immune checkpoint genes, and oncogenes. Moreover, the ROC curve analysis showed that PER3 could accurately differentiate between GBM tissues and adjacent normal tissues. To further validate the neurotoxicity of DEHP, we analyzed the effects of DEHP exposure on zebrafish development and PER3 expression by behavioral experiments and molecular biology. The results showed that exposure to DEHP substantially altered both the behavioral responses and the gene expression profiles within the brain tissues of zebrafish. PCR results indicate that the expression of circadian rhythm factor PER3 was significantly reduced in the brains of zebrafish in the exposed group, and circadian dysregulation had a certain promoting effect on the development of glioma. The aim of this work was to investigate the potential effects of DEHP contamination in a water environment on organism brain development. It was demonstrated that PER3 is an effective early diagnostic marker, which is of great significance in the diagnosis and clinical prognosis of glioma, and that DEHP exposure can lead to a significant reduction in PER3 expression in zebrafish brain tissue. This study further proved that DEHP has a potential carcinogenic effect, which adds scientific evidence to the carcinogenicity study of DEHP. |
| format | Article |
| id | doaj-art-3df3742e5bef4416848162f79b09a2b7 |
| institution | DOAJ |
| issn | 2305-6304 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
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| series | Toxics |
| spelling | doaj-art-3df3742e5bef4416848162f79b09a2b72025-08-20T02:57:29ZengMDPI AGToxics2305-63042024-11-01121283510.3390/toxics12120835DEHP-Induced Glioblastoma in Zebrafish Is Associated with Circadian Dysregulation of PER3Shuhui Men0Jiayun Xu1Zhanhong Yang2Zhenguang Yan3State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, ChinaNingbo Clinical Pathology Diagnosis Center, Ningbo 315021, ChinaEnvironmental Standards Institute of Ministry of Ecology and Environment of the People’s Republic of China, Beijing 100012, ChinaState Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, ChinaDEHP is a plasticizer that is widely found in our water environment and poses a significant risk to the environment and human health. Long-term exposure to DEHP can cause endocrine disruption and interfere with the organism’s normal functioning. In order to explore the potential effects of DEHP on the development of biological brain tissues, this study used bioinformatics analysis to confirm the diagnostic and prognostic value of PER3 in gliomas and further validated the neurotoxicity of DEHP using methods such as behavioral experiments and molecular biology in zebrafish. The experimental findings revealed that the expression level of PER3 in diseased tissues was significantly lower than that in the control group. In addition, the expression level of PER3 was significantly correlated with immune cell infiltration, immune checkpoint genes, and oncogenes. Moreover, the ROC curve analysis showed that PER3 could accurately differentiate between GBM tissues and adjacent normal tissues. To further validate the neurotoxicity of DEHP, we analyzed the effects of DEHP exposure on zebrafish development and PER3 expression by behavioral experiments and molecular biology. The results showed that exposure to DEHP substantially altered both the behavioral responses and the gene expression profiles within the brain tissues of zebrafish. PCR results indicate that the expression of circadian rhythm factor PER3 was significantly reduced in the brains of zebrafish in the exposed group, and circadian dysregulation had a certain promoting effect on the development of glioma. The aim of this work was to investigate the potential effects of DEHP contamination in a water environment on organism brain development. It was demonstrated that PER3 is an effective early diagnostic marker, which is of great significance in the diagnosis and clinical prognosis of glioma, and that DEHP exposure can lead to a significant reduction in PER3 expression in zebrafish brain tissue. This study further proved that DEHP has a potential carcinogenic effect, which adds scientific evidence to the carcinogenicity study of DEHP.https://www.mdpi.com/2305-6304/12/12/835DEHPcarcinogenic effectcircadian rhythmPeriod circadian regulator 3 |
| spellingShingle | Shuhui Men Jiayun Xu Zhanhong Yang Zhenguang Yan DEHP-Induced Glioblastoma in Zebrafish Is Associated with Circadian Dysregulation of PER3 Toxics DEHP carcinogenic effect circadian rhythm Period circadian regulator 3 |
| title | DEHP-Induced Glioblastoma in Zebrafish Is Associated with Circadian Dysregulation of PER3 |
| title_full | DEHP-Induced Glioblastoma in Zebrafish Is Associated with Circadian Dysregulation of PER3 |
| title_fullStr | DEHP-Induced Glioblastoma in Zebrafish Is Associated with Circadian Dysregulation of PER3 |
| title_full_unstemmed | DEHP-Induced Glioblastoma in Zebrafish Is Associated with Circadian Dysregulation of PER3 |
| title_short | DEHP-Induced Glioblastoma in Zebrafish Is Associated with Circadian Dysregulation of PER3 |
| title_sort | dehp induced glioblastoma in zebrafish is associated with circadian dysregulation of per3 |
| topic | DEHP carcinogenic effect circadian rhythm Period circadian regulator 3 |
| url | https://www.mdpi.com/2305-6304/12/12/835 |
| work_keys_str_mv | AT shuhuimen dehpinducedglioblastomainzebrafishisassociatedwithcircadiandysregulationofper3 AT jiayunxu dehpinducedglioblastomainzebrafishisassociatedwithcircadiandysregulationofper3 AT zhanhongyang dehpinducedglioblastomainzebrafishisassociatedwithcircadiandysregulationofper3 AT zhenguangyan dehpinducedglioblastomainzebrafishisassociatedwithcircadiandysregulationofper3 |