Polycyclic aromatic hydrocarbons promote tumorigenesis of gallbladder cancer via aryl hydrocarbon Receptor-HEGBC positive feedback axis
Summary: Gallbladder cancer (GBC) is a highly aggressive tumor associated with risk factors, such as chronic infection, gallstones, and exposure to harmful chemicals. Our study explores the role of polycyclic aromatic hydrocarbons (PAHs) and long noncoding RNA HEGBC in GBC progression. We found that...
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Elsevier
2025-05-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225007667 |
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| author | Lei Yuan Yumeng Zhang Jianguo Xu Feng Liu Yingchao Liang Beili Wang Meihong Wu Zhiyuan Fan Liang Yang |
| author_facet | Lei Yuan Yumeng Zhang Jianguo Xu Feng Liu Yingchao Liang Beili Wang Meihong Wu Zhiyuan Fan Liang Yang |
| author_sort | Lei Yuan |
| collection | DOAJ |
| description | Summary: Gallbladder cancer (GBC) is a highly aggressive tumor associated with risk factors, such as chronic infection, gallstones, and exposure to harmful chemicals. Our study explores the role of polycyclic aromatic hydrocarbons (PAHs) and long noncoding RNA HEGBC in GBC progression. We found that PAHs activate the aryl hydrocarbon receptor (AhR), which enhances HEGBC expression and promotes GBC cell proliferation, invasion, and metastasis both in vitro and in vivo. Mechanistically, AhR binds to the HEGBC promoter, establishing a positive feedback loop that further activates AhR transcription. Moreover, CYP1A1 was identified as a key downstream effector of PAHs-AhR/HEGBC-mediated proliferation, migration, and invasion of GBC cells in vitro and in vivo. These findings provide the integrative view of a molecular mechanism loop for regulating the malignant progression of GBC centered by PAHs/AhR/HEGBC, which represents a promising strategy for the treatment of GBC. |
| format | Article |
| id | doaj-art-c46cbd811a834e5d8ec6fb4d4beea4ad |
| institution | OA Journals |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-c46cbd811a834e5d8ec6fb4d4beea4ad2025-08-20T01:48:50ZengElsevieriScience2589-00422025-05-0128511250510.1016/j.isci.2025.112505Polycyclic aromatic hydrocarbons promote tumorigenesis of gallbladder cancer via aryl hydrocarbon Receptor-HEGBC positive feedback axisLei Yuan0Yumeng Zhang1Jianguo Xu2Feng Liu3Yingchao Liang4Beili Wang5Meihong Wu6Zhiyuan Fan7Liang Yang8Department of Hepatobiliary Surgery, Quzhou People’s Hospital, 100 Minjiang Main Road, Quzhou, Zhejiang 324000, ChinaDepartment of Radiation Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 201204, ChinaDepartment of Plastic Surgery, Changhai Hospital, Naval Medical University, Shanghai 200433, ChinaDepartment of Scientific Research, Novel-Intel Biotech (Nanjing) Co., Ltd, Nanjing 211899, ChinaDepartment of Radiation Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 201204, ChinaDepartment of Radiation Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 201204, ChinaDepartment of Oncology, Changhai Hospital, Naval Medical University, Shanghai 200433, China; Corresponding authorDepartment of Breast Surgery, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 201204, China; Corresponding authorDepartment of Hepatobiliary Surgery, Quzhou People’s Hospital, 100 Minjiang Main Road, Quzhou, Zhejiang 324000, China; Department of Radiation Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 201204, China; Corresponding authorSummary: Gallbladder cancer (GBC) is a highly aggressive tumor associated with risk factors, such as chronic infection, gallstones, and exposure to harmful chemicals. Our study explores the role of polycyclic aromatic hydrocarbons (PAHs) and long noncoding RNA HEGBC in GBC progression. We found that PAHs activate the aryl hydrocarbon receptor (AhR), which enhances HEGBC expression and promotes GBC cell proliferation, invasion, and metastasis both in vitro and in vivo. Mechanistically, AhR binds to the HEGBC promoter, establishing a positive feedback loop that further activates AhR transcription. Moreover, CYP1A1 was identified as a key downstream effector of PAHs-AhR/HEGBC-mediated proliferation, migration, and invasion of GBC cells in vitro and in vivo. These findings provide the integrative view of a molecular mechanism loop for regulating the malignant progression of GBC centered by PAHs/AhR/HEGBC, which represents a promising strategy for the treatment of GBC.http://www.sciencedirect.com/science/article/pii/S2589004225007667biological sciencescancer systems biologyhealth sciencesinternal medicinemedical specialtymedicine |
| spellingShingle | Lei Yuan Yumeng Zhang Jianguo Xu Feng Liu Yingchao Liang Beili Wang Meihong Wu Zhiyuan Fan Liang Yang Polycyclic aromatic hydrocarbons promote tumorigenesis of gallbladder cancer via aryl hydrocarbon Receptor-HEGBC positive feedback axis iScience biological sciences cancer systems biology health sciences internal medicine medical specialty medicine |
| title | Polycyclic aromatic hydrocarbons promote tumorigenesis of gallbladder cancer via aryl hydrocarbon Receptor-HEGBC positive feedback axis |
| title_full | Polycyclic aromatic hydrocarbons promote tumorigenesis of gallbladder cancer via aryl hydrocarbon Receptor-HEGBC positive feedback axis |
| title_fullStr | Polycyclic aromatic hydrocarbons promote tumorigenesis of gallbladder cancer via aryl hydrocarbon Receptor-HEGBC positive feedback axis |
| title_full_unstemmed | Polycyclic aromatic hydrocarbons promote tumorigenesis of gallbladder cancer via aryl hydrocarbon Receptor-HEGBC positive feedback axis |
| title_short | Polycyclic aromatic hydrocarbons promote tumorigenesis of gallbladder cancer via aryl hydrocarbon Receptor-HEGBC positive feedback axis |
| title_sort | polycyclic aromatic hydrocarbons promote tumorigenesis of gallbladder cancer via aryl hydrocarbon receptor hegbc positive feedback axis |
| topic | biological sciences cancer systems biology health sciences internal medicine medical specialty medicine |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225007667 |
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