Identification of AHR and hypoxia co-regulated immune target genes as potential factors of inflammation-driven oncogenesis
The transcription factors AHR and HIFs dimerize with the common co-activator ARNT during adaptive responses to xenobiotic exposure and oxygen tension. This cross-talk may subsequently modulate inflammation and/or physiological adaptation via immune cellular survival and maturation. Dysregulation of...
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| Other Authors: | |
| Format: | Thesis |
| Language: | English |
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2015
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| Online Access: | http://hdl.handle.net/10356/65300 |
| _version_ | 1826116214673375232 |
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| author | Zaiden, Norazean |
| author2 | Lee Kian Leong |
| author_facet | Lee Kian Leong Zaiden, Norazean |
| author_sort | Zaiden, Norazean |
| collection | NTU |
| description | The transcription factors AHR and HIFs dimerize with the common co-activator ARNT during adaptive responses to xenobiotic exposure and oxygen tension. This cross-talk may subsequently modulate inflammation and/or physiological adaptation via immune cellular survival and maturation. Dysregulation of AHR and HIF pathways can cause chronic inflammation leading to oncogenesis, thus we hypothesized that AHR and hypoxia signaling co-operate in potentiating inflammation-driven oncogenesis. To address this, we analyzed AHR-mediated transcriptional responses in three frequently xenobiotic-exposed study models (murine liver, human keratinocytes, human intestinal epithelial cells), especially in the intestine, where AHR and hypoxia signaling constantly co-exist. Although AHR signaling is evolutionary conserved, we find that the AHR mediates diverse responses in a cell type- and species-dependent manner. Concurrent activation with hypoxia signaling in intestinal cells indicate a promotion of chronic inflammation through down-regulation of numerous anti-inflammatory target genes, and up-regulation of pro-inflammatory genes such as PTGS2, GZMB, and MMP1. |
| first_indexed | 2024-10-01T04:07:40Z |
| format | Thesis |
| id | ntu-10356/65300 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T04:07:40Z |
| publishDate | 2015 |
| record_format | dspace |
| spelling | ntu-10356/653002023-02-28T18:36:48Z Identification of AHR and hypoxia co-regulated immune target genes as potential factors of inflammation-driven oncogenesis Zaiden, Norazean Lee Kian Leong Lorenz Poellinger School of Biological Sciences Cancer Science Institute of Singapore DRNTU::Science::Biological sciences::Molecular biology The transcription factors AHR and HIFs dimerize with the common co-activator ARNT during adaptive responses to xenobiotic exposure and oxygen tension. This cross-talk may subsequently modulate inflammation and/or physiological adaptation via immune cellular survival and maturation. Dysregulation of AHR and HIF pathways can cause chronic inflammation leading to oncogenesis, thus we hypothesized that AHR and hypoxia signaling co-operate in potentiating inflammation-driven oncogenesis. To address this, we analyzed AHR-mediated transcriptional responses in three frequently xenobiotic-exposed study models (murine liver, human keratinocytes, human intestinal epithelial cells), especially in the intestine, where AHR and hypoxia signaling constantly co-exist. Although AHR signaling is evolutionary conserved, we find that the AHR mediates diverse responses in a cell type- and species-dependent manner. Concurrent activation with hypoxia signaling in intestinal cells indicate a promotion of chronic inflammation through down-regulation of numerous anti-inflammatory target genes, and up-regulation of pro-inflammatory genes such as PTGS2, GZMB, and MMP1. Master of Science 2015-07-10T07:51:31Z 2015-07-10T07:51:31Z 2015 2015 Thesis Zaiden, N. (2015). Identification of AHR and hypoxia co-regulated immune target genes as potential factors of inflammation-driven oncogenesis. Master's thesis, Nanyang Technological University, Singapore. http://hdl.handle.net/10356/65300 en 133 p. application/pdf |
| spellingShingle | DRNTU::Science::Biological sciences::Molecular biology Zaiden, Norazean Identification of AHR and hypoxia co-regulated immune target genes as potential factors of inflammation-driven oncogenesis |
| title | Identification of AHR and hypoxia co-regulated immune target genes as potential factors of inflammation-driven oncogenesis |
| title_full | Identification of AHR and hypoxia co-regulated immune target genes as potential factors of inflammation-driven oncogenesis |
| title_fullStr | Identification of AHR and hypoxia co-regulated immune target genes as potential factors of inflammation-driven oncogenesis |
| title_full_unstemmed | Identification of AHR and hypoxia co-regulated immune target genes as potential factors of inflammation-driven oncogenesis |
| title_short | Identification of AHR and hypoxia co-regulated immune target genes as potential factors of inflammation-driven oncogenesis |
| title_sort | identification of ahr and hypoxia co regulated immune target genes as potential factors of inflammation driven oncogenesis |
| topic | DRNTU::Science::Biological sciences::Molecular biology |
| url | http://hdl.handle.net/10356/65300 |
| work_keys_str_mv | AT zaidennorazean identificationofahrandhypoxiacoregulatedimmunetargetgenesaspotentialfactorsofinflammationdrivenoncogenesis |