Ferroptosis is governed by differential regulation of transcription in liver cancer.

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.

journal_name

Redox Biol

journal_title

Redox biology

authors

Zhang X,Du L,Qiao Y,Zhang X,Zheng W,Wu Q,Chen Y,Zhu G,Liu Y,Bian Z,Guo S,Yang Y,Ma L,Yu Y,Pan Q,Sun F,Wang J

doi

10.1016/j.redox.2019.101211

subject

Has Abstract

pub_date

2019-06-01 00:00:00

pages

101211

issn

2213-2317

pii

S2213-2317(19)30404-5

journal_volume

24

pub_type

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