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Ferroptosis is governed by differential regulation of transcription in liver cancer
Open accessAbstract
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. • Opposite gene expression profiles trigged by ferroptosis are identified. • Reduction of GSH is the major cause of inducing ferroptosis in liver cancer cells. • Genes related to ferroptosis are controlled by transcription factors HIC1 and HNF4A. • Stimulation of ferroptosis breaks the balance between HIC1 and HNF4A. • Lower HIC1 with higher HNF4A has poorer clinical outcomes in liver cancer patients.
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Cites
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Glutaminolysis and transferrin regulate ferroptosis
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Cited by
Ferroptosis: machinery and regulation
Chen, X., Li, J., Kang, R., Klionsky, D. J., & Tang, D. (2021) · Autophagy · doi:10.1080/15548627.2020.1810918 · Cited by 2,099
The application of Ferroptosis in diseases
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Emerging mechanisms and targeted therapy of ferroptosis in cancer
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Metadata
- 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.
- Venue
- Redox Biology
- Publisher
- Elsevier BV
- Published
- 2019-06
- Volume
- 24
- Pages
- 101211
- ISSN
- 2213-2317 (ISSN-L)
- OpenAlex
- W2944417415
- Cited by
- 186
- References
- 11
- FWCI
- 17.79
- Type
- journal article
- Language
- en
- Status
- Retracted
- Open access
- gold
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- 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. (2019). Ferroptosis is governed by differential regulation of transcription in liver cancer. Redox Biology. https://doi.org/10.1016/j.redox.2019.101211
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