Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10147)
Regulator Name Zinc finger E-box-binding homeobox 1 (ZEB1)
Synonyms
AREB6, TCF8; NIL-2-A zinc finger protein; Negative regulator of IL2; Transcription factor 8
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Gene Name ZEB1
Gene ID 6935
Regulator Type Protein coding
Uniprot ID P37275
Sequence
MADGPRCKRRKQANPRRNNVTNYNTVVETNSDSDDEDKLHIVEEESVTDAADCEGVPEDD
LPTDQTVLPGRSSEREGNAKNCWEDDRKEGQEILGPEAQADEAGCTVKDDECESDAENEQ
NHDPNVEEFLQQQDTAVIFPEAPEEDQRQGTPEASGHDENGTPDAFSQLLTCPYCDRGYK
RFTSLKEHIKYRHEKNEDNFSCSLCSYTFAYRTQLERHMTSHKSGRDQRHVTQSGCNRKF
KCTECGKAFKYKHHLKEHLRIHSGEKPYECPNCKKRFSHSGSYSSHISSKKCISLIPVNG
RPRTGLKTSQCSSPSLSASPGSPTRPQIRQKIENKPLQEQLSVNQIKTEPVDYEFKPIVV
ASGINCSTPLQNGVFTGGGPLQATSSPQGMVQAVVLPTVGLVSPISINLSDIQNVLKVAV
DGNVIRQVLENNQANLASKEQETINASPIQQGGHSVISAISLPLVDQDGTTKIIINYSLE
QPSQLQVVPQNLKKENPVATNSCKSEKLPEDLTVKSEKDKSFEGGVNDSTCLLCDDCPGD
INALPELKHYDLKQPTQPPPLPAAEAEKPESSVSSATGDGNLSPSQPPLKNLLSLLKAYY
ALNAQPSAEELSKIADSVNLPLDVVKKWFEKMQAGQISVQSSEPSSPEPGKVNIPAKNND
QPQSANANEPQDSTVNLQSPLKMTNSPVLPVGSTTNGSRSSTPSPSPLNLSSSRNTQGYL
YTAEGAQEEPQVEPLDLSLPKQQGELLERSTITSVYQNSVYSVQEEPLNLSCAKKEPQKD
SCVTDSEPVVNVIPPSANPINIAIPTVTAQLPTIVAIADQNSVPCLRALAANKQTILIPQ
VAYTYSTTVSPAVQEPPLKVIQPNGNQDERQDTSSEGVSNVEDQNDSDSTPPKKKMRKTE
NGMYACDLCDKIFQKSSSLLRHKYEHTGKRPHECGICKKAFKHKHHLIEHMRLHSGEKPY
QCDKCGKRFSHSGSYSQHMNHRYSYCKREAEERDSTEQEEAGPEILSNEHVGARASPSQG
DSDERESLTREEDEDSEKEEEEEDKEMEELQEEKECEKPQGDEEEEEEEEEVEEEEVEEA
ENEGEEAKTEGLMKDDRAESQASSLGQKVGESSEQVSEEKTNEA

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Family Delta-EF1/ZFH-1 C2H2-type zinc-finger family
Function
Acts as a transcriptional repressor. Inhibits interleukin-2 (IL-2) gene expression. Enhances or represses the promoter activity of the ATP1A1 gene depending on the quantity of cDNA and on the cell type. Represses E-cadherin promoter and induces an epithelial-mesenchymal transition (EMT) by recruiting SMARCA4/BRG1. Represses BCL6 transcription in the presence of the corepressor CTBP1. Positively regulates neuronal differentiation. Represses RCOR1 transcription activation during neurogenesis. Represses transcription by binding to the E box (5'-CANNTG-3'). Promotes tumorigenicity by repressing stemness-inhibiting microRNAs.

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HGNC ID
HGNC:11642
KEGG ID hsa:6935
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
ZEB1 can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
Browse Target
Browse Disease
Phospholipid hydroperoxide glutathione peroxidase (GPX4) [Suppressor]
 Target Info 
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Suppressor
Responsed Disease Osteosarcoma ICD-11: 2B51
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell migration
Cell invasion
In Vitro Model
 143B cells Osteosarcoma Homo sapiens CVCL_2270
SW1353 cells Bone chondrosarcoma Homo sapiens CVCL_0543
MG-63 cells Osteosarcoma Homo sapiens CVCL_0426
SAOS-2 cells Osteosarcoma Homo sapiens CVCL_0548
U2OS cells Osteosarcoma Homo sapiens CVCL_0042
HOB (Human normal osteoblastic cells)
In Vivo Model
The OS model of nude mice was constructed using the CDTX model. After transfection, the h143B cells were prepared into a single-cell suspension and subcutaneously injected into the left proximal tibia of 36 (3 mice per group) 4-weeks-old nude mice (1 x 107 cells per mouse).

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Response regulation MiR-144-3p can induce the occurrence of ferroptosis by negatively regulating the expression of ZEB1, thereby inhibiting the proliferation, migration, and invasion of osteosarcoma (OS) cells. The overexpression of ZEB1 caused the lower expression level of ACSL4 and higher expression level of xCT and GPX4.
Experiment 2 Reporting the Ferroptosis Target of This Regulator [2]
Target for Ferroptosis Suppressor
Responsed Disease Fibrosarcoma ICD-11: 2B53
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
LOX-IMVI cells Melanoma Homo sapiens CVCL_1381
WI-38 cells Normal Homo sapiens CVCL_0579
RKN cells Ovarian leiomyosarcoma Homo sapiens CVCL_3156
KP-4 cells Pancreatic carcinoma Homo sapiens CVCL_1338
HUVECs (Human umbilical vein endothelial cells)
BJeH (Human foreskin fibroblasts)
MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
NCI-H358 cells Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1559
HCC4006 cells Lung adenocarcinoma Homo sapiens CVCL_1269
M000921 cells Melanoma Homo sapiens CVCL_S808
M980513 cells Melanoma Homo sapiens CVCL_S675
AA01 (Pancreatic cancer cells)
AA02 (Pancreatic cancer cells)
In Vivo Model
Xenografts for LOXIMVI sgEGFP (WT) and LOXIMVI sgGPX4 (KO) cells were established by injecting 10 million cells in a 1:1 PBS:Matrigel mixture containing 2.5 uM ferrostatin-1 into the flanks of athymic mice (NRC Nude, Taconic). Animals were dosed daily with 2 mg kg-1 ferrostatin-1 by intraperitoneal injections. Tumour volume was measured twice a week.

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Response regulation The resulting dependency of ZEB1-high cells on lipid-peroxidase activity is most effectively exploited by direct inhibition of GPX4 in Fibrosarcoma.
Long-chain-fatty-acid--CoA ligase 4 (ACSL4) [Driver]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Driver
Responsed Disease Osteosarcoma ICD-11: 2B51
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell migration
Cell invasion
In Vitro Model
 143B cells Osteosarcoma Homo sapiens CVCL_2270
SW1353 cells Bone chondrosarcoma Homo sapiens CVCL_0543
MG-63 cells Osteosarcoma Homo sapiens CVCL_0426
SAOS-2 cells Osteosarcoma Homo sapiens CVCL_0548
U2OS cells Osteosarcoma Homo sapiens CVCL_0042
HOB (Human normal osteoblastic cells)
In Vivo Model
The OS model of nude mice was constructed using the CDTX model. After transfection, the h143B cells were prepared into a single-cell suspension and subcutaneously injected into the left proximal tibia of 36 (3 mice per group) 4-weeks-old nude mice (1 x 107 cells per mouse).

    Click to Show/Hide
Response regulation MiR-144-3p can induce the occurrence of ferroptosis by negatively regulating the expression of ZEB1, thereby inhibiting the proliferation, migration, and invasion of osteosarcoma (OS) cells. The overexpression of ZEB1 caused the lower expression level of ACSL4 and higher expression level of xCT and GPX4.
Osteosarcoma [ICD-11: 2B51]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Zinc finger E-box-binding homeobox 1 (ZEB1) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell migration
Cell invasion
In Vitro Model
 143B cells Osteosarcoma Homo sapiens CVCL_2270
SW1353 cells Bone chondrosarcoma Homo sapiens CVCL_0543
MG-63 cells Osteosarcoma Homo sapiens CVCL_0426
SAOS-2 cells Osteosarcoma Homo sapiens CVCL_0548
U2OS cells Osteosarcoma Homo sapiens CVCL_0042
HOB (Human normal osteoblastic cells)
In Vivo Model
The OS model of nude mice was constructed using the CDTX model. After transfection, the h143B cells were prepared into a single-cell suspension and subcutaneously injected into the left proximal tibia of 36 (3 mice per group) 4-weeks-old nude mice (1 x 107 cells per mouse).

    Click to Show/Hide
Response regulation MiR-144-3p can induce the occurrence of ferroptosis by negatively regulating the expression of ZEB1, thereby inhibiting the proliferation, migration, and invasion of osteosarcoma (OS) cells. The overexpression of ZEB1 caused the lower expression level of ACSL4 and higher expression level of xCT and GPX4.
Experiment 2 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Zinc finger E-box-binding homeobox 1 (ZEB1) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell migration
Cell invasion
In Vitro Model
 143B cells Osteosarcoma Homo sapiens CVCL_2270
SW1353 cells Bone chondrosarcoma Homo sapiens CVCL_0543
MG-63 cells Osteosarcoma Homo sapiens CVCL_0426
SAOS-2 cells Osteosarcoma Homo sapiens CVCL_0548
U2OS cells Osteosarcoma Homo sapiens CVCL_0042
HOB (Human normal osteoblastic cells)
In Vivo Model
The OS model of nude mice was constructed using the CDTX model. After transfection, the h143B cells were prepared into a single-cell suspension and subcutaneously injected into the left proximal tibia of 36 (3 mice per group) 4-weeks-old nude mice (1 x 107 cells per mouse).

    Click to Show/Hide
Response regulation MiR-144-3p can induce the occurrence of ferroptosis by negatively regulating the expression of ZEB1, thereby inhibiting the proliferation, migration, and invasion of osteosarcoma (OS) cells. The overexpression of ZEB1 caused the lower expression level of ACSL4 and higher expression level of xCT and GPX4.
Fibrosarcoma [ICD-11: 2B53]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Zinc finger E-box-binding homeobox 1 (ZEB1) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
LOX-IMVI cells Melanoma Homo sapiens CVCL_1381
WI-38 cells Normal Homo sapiens CVCL_0579
RKN cells Ovarian leiomyosarcoma Homo sapiens CVCL_3156
KP-4 cells Pancreatic carcinoma Homo sapiens CVCL_1338
HUVECs (Human umbilical vein endothelial cells)
BJeH (Human foreskin fibroblasts)
MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
NCI-H358 cells Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1559
HCC4006 cells Lung adenocarcinoma Homo sapiens CVCL_1269
M000921 cells Melanoma Homo sapiens CVCL_S808
M980513 cells Melanoma Homo sapiens CVCL_S675
AA01 (Pancreatic cancer cells)
AA02 (Pancreatic cancer cells)
In Vivo Model
Xenografts for LOXIMVI sgEGFP (WT) and LOXIMVI sgGPX4 (KO) cells were established by injecting 10 million cells in a 1:1 PBS:Matrigel mixture containing 2.5 uM ferrostatin-1 into the flanks of athymic mice (NRC Nude, Taconic). Animals were dosed daily with 2 mg kg-1 ferrostatin-1 by intraperitoneal injections. Tumour volume was measured twice a week.

    Click to Show/Hide
Response regulation The resulting dependency of ZEB1-high cells on lipid-peroxidase activity is most effectively exploited by direct inhibition of GPX4 in Fibrosarcoma.
References
Ref 1 Exosome-mediated miR-144-3p promotes ferroptosis to inhibit osteosarcoma proliferation, migration, and invasion through regulating ZEB1. Mol Cancer. 2023 Jul 17;22(1):113. doi: 10.1186/s12943-023-01804-z.
Ref 2 Dependency of a therapy-resistant state of cancer cells on a lipid peroxidase pathway. Nature. 2017 Jul 27;547(7664):453-457. doi: 10.1038/nature23007. Epub 2017 Jul 5.