Ferroptosis is governed by differential regulation of transcription in liver cancer
Ferroptosis is an outcome of metabolic disorders and closely linked to liver cancer. However, the mechanism underlying the fine regulation of ferroptosis in liver cancer remains unclear. Here, we have identified two categories of genes: ferroptosis up-regulated factors (FUF) and ferroptosis down-reg...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-06-01
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| Series: | Redox Biology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231719304045 |
| _version_ | 1818489628703850496 |
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| author | Xiao Zhang Lutao Du Yongxia Qiao Xiaobai Zhang Weisheng Zheng Qi Wu Yan Chen Guoqing Zhu Ya Liu Zhixuan Bian Susu Guo Yueyue Yang Lifang Ma Yongchun Yu Qiuhui Pan Fenyong Sun Jiayi Wang |
| author_facet | Xiao Zhang Lutao Du Yongxia Qiao Xiaobai Zhang Weisheng Zheng Qi Wu Yan Chen Guoqing Zhu Ya Liu Zhixuan Bian Susu Guo Yueyue Yang Lifang Ma Yongchun Yu Qiuhui Pan Fenyong Sun Jiayi Wang |
| author_sort | Xiao Zhang |
| collection | DOAJ |
| description | Ferroptosis is an outcome of metabolic disorders and closely linked to liver cancer. However, the mechanism underlying the fine regulation of ferroptosis in liver cancer remains unclear. Here, we have identified two categories of genes: ferroptosis up-regulated factors (FUF) and ferroptosis down-regulated factors (FDF), which stimulate and suppress ferroptosis by affecting the synthesis of GSH. Furthermore, FUF are controlled by one transcription factor HIC1, while FDF controlled by another transcription factor HNF4A. Occurrence of ferroptosis might depend on the histone acetyltransferase KAT2B. Upon stimulation of ferroptosis, dissociation of KAT2B prevents HNF4A from binding to the FDF promoter. This effect happens prior to the recruitment of KAT2B to the FUF promoter, which facilitates HIC1 binding to transcribe FUF. Clinically, HIC1 and HNF4A conversely correlate with tumor stage in liver cancer. Patients with lower HIC1 and higher HNF4A exhibit poorer prognostic outcomes. Disrupting the balance between HIC1 and HNF4A might be helpful in treating liver cancer. Keywords: HIC1, HNF4A, GSH, Acetyltransferase, Promoter, Metabolism |
| first_indexed | 2024-12-10T17:06:19Z |
| format | Article |
| id | doaj.art-05aecdd55a59484c9d0026ae0d3d2048 |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-12-10T17:06:19Z |
| publishDate | 2019-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-05aecdd55a59484c9d0026ae0d3d20482022-12-22T01:40:26ZengElsevierRedox Biology2213-23172019-06-0124Ferroptosis is governed by differential regulation of transcription in liver cancerXiao Zhang0Lutao Du1Yongxia Qiao2Xiaobai Zhang3Weisheng Zheng4Qi Wu5Yan Chen6Guoqing Zhu7Ya Liu8Zhixuan Bian9Susu Guo10Yueyue Yang11Lifang Ma12Yongchun Yu13Qiuhui Pan14Fenyong Sun15Jiayi Wang16Department of Clinical Laboratory, Shanghai Tenth People's Hospital of Tongji University, Shanghai, 200072, ChinaDepartment of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, 250033, Shandong province, ChinaSchool of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, ChinaSchool of Life Science and Technology, Shanghai Key Laboratory of Signaling and Disease Research, Tongji University, Shanghai, 200092, ChinaSchool of Life Science and Technology, Shanghai Key Laboratory of Signaling and Disease Research, Tongji University, Shanghai, 200092, ChinaDepartment of Clinical Laboratory, Shanghai Tenth People's Hospital of Tongji University, Shanghai, 200072, ChinaDepartment of Clinical Laboratory, Shanghai Tenth People's Hospital of Tongji University, Shanghai, 200072, ChinaDepartment of Clinical Laboratory, Shanghai Tenth People's Hospital of Tongji University, Shanghai, 200072, ChinaDepartment of Clinical Laboratory, Shanghai Tenth People's Hospital of Tongji University, Shanghai, 200072, ChinaDepartment of Laboratory Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, ChinaDepartment of Clinical Laboratory, Shanghai Tenth People's Hospital of Tongji University, Shanghai, 200072, ChinaDepartment of Clinical Laboratory, Shanghai Tenth People's Hospital of Tongji University, Shanghai, 200072, ChinaShanghai Institute of Thoracic Tumors, Shanghai Chest Hospital, Shanghai, 200030, ChinaShanghai Chest Hospital, Shanghai, 200030, ChinaDepartment of Laboratory Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, China; Corresponding author.Department of Clinical Laboratory, Shanghai Tenth People's Hospital of Tongji University, Shanghai, 200072, China; Corresponding author.Department of Clinical Laboratory, Shanghai Tenth People's Hospital of Tongji University, Shanghai, 200072, China; Advanced Institute of Translational Medicine, Tongji University, Shanghai, 200092, China; Corresponding author. Department of Clinical Laboratory, Shanghai Tenth People's Hospital of Tongji University, Shanghai, 200072, China.Ferroptosis is an outcome of metabolic disorders and closely linked to liver cancer. However, the mechanism underlying the fine regulation of ferroptosis in liver cancer remains unclear. Here, we have identified two categories of genes: ferroptosis up-regulated factors (FUF) and ferroptosis down-regulated factors (FDF), which stimulate and suppress ferroptosis by affecting the synthesis of GSH. Furthermore, FUF are controlled by one transcription factor HIC1, while FDF controlled by another transcription factor HNF4A. Occurrence of ferroptosis might depend on the histone acetyltransferase KAT2B. Upon stimulation of ferroptosis, dissociation of KAT2B prevents HNF4A from binding to the FDF promoter. This effect happens prior to the recruitment of KAT2B to the FUF promoter, which facilitates HIC1 binding to transcribe FUF. Clinically, HIC1 and HNF4A conversely correlate with tumor stage in liver cancer. Patients with lower HIC1 and higher HNF4A exhibit poorer prognostic outcomes. Disrupting the balance between HIC1 and HNF4A might be helpful in treating liver cancer. Keywords: HIC1, HNF4A, GSH, Acetyltransferase, Promoter, Metabolismhttp://www.sciencedirect.com/science/article/pii/S2213231719304045 |
| spellingShingle | Xiao Zhang Lutao Du Yongxia Qiao Xiaobai Zhang Weisheng Zheng Qi Wu Yan Chen Guoqing Zhu Ya Liu Zhixuan Bian Susu Guo Yueyue Yang Lifang Ma Yongchun Yu Qiuhui Pan Fenyong Sun Jiayi Wang Ferroptosis is governed by differential regulation of transcription in liver cancer Redox Biology |
| title | Ferroptosis is governed by differential regulation of transcription in liver cancer |
| title_full | Ferroptosis is governed by differential regulation of transcription in liver cancer |
| title_fullStr | Ferroptosis is governed by differential regulation of transcription in liver cancer |
| title_full_unstemmed | Ferroptosis is governed by differential regulation of transcription in liver cancer |
| title_short | Ferroptosis is governed by differential regulation of transcription in liver cancer |
| title_sort | ferroptosis is governed by differential regulation of transcription in liver cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2213231719304045 |
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