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Ferroptosis is governed by differential regulation of transcription in liver cancer
- Source :
- Redox Biology, Vol 24, Iss, Pp-(2019)
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- 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
- Subjects :
- 0301 basic medicine
endocrine system
Transcription, Genetic
Clinical Biochemistry
Stimulation
Biology
Models, Biological
Biochemistry
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Transcription (biology)
medicine
Animals
Ferroptosis
Humans
Promoter Regions, Genetic
lcsh:QH301-705.5
Gene
Transcription factor
Mice, Knockout
lcsh:R5-920
Liver Neoplasms
Organic Chemistry
Histone Acetyltransferase KAT2B
Glutathione
medicine.disease
Gene Expression Regulation, Neoplastic
Disease Models, Animal
Cell Transformation, Neoplastic
030104 developmental biology
lcsh:Biology (General)
chemistry
Acetyltransferase
Cancer research
Female
lcsh:Medicine (General)
Liver cancer
030217 neurology & neurosurgery
Research Paper
Subjects
Details
- ISSN :
- 22132317
- Volume :
- 24
- Database :
- OpenAIRE
- Journal :
- Redox Biology
- Accession number :
- edsair.doi.dedup.....c22ba4f1eaec587e3d6d9ea12452576d