Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10101)
Regulator Name Mucin-1 (MUC1)
Synonyms
PUM; Breast carcinoma-associated antigen DF3; Cancer antigen 15-3; Carcinoma-associated mucin; Episialin; H23AG; Krebs von den Lungen-6; PEMT; Peanut-reactive urinary mucin; Polymorphic epithelial mucin; Tumor-associated epithelial membrane antigen; Tumor-associated mucin; CD_antigen=CD227
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Gene Name MUC1
Gene ID 4582
Regulator Type Protein coding
Uniprot ID P15941
Sequence
MTPGTQSPFFLLLLLTVLTVVTGSGHASSTPGGEKETSATQRSSVPSSTEKNAVSMTSSV
LSSHSPGSGSSTTQGQDVTLAPATEPASGSAATWGQDVTSVPVTRPALGSTTPPAHDVTS
APDNKPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDNRPALGSTAPPVHNVTS
ASGSASGSASTLVHNGTSARATTTPASKSTPFSIPSHHSDTPTTLASHSTKTDASSTHHS
SVPPLTSSNHSTSPQLSTGVSFFFLSFHISNLQFNSSLEDPSTDYYQELQRDISEMFLQI
YKQGGFLGLSNIKFRPGSVVVQLTLAFREGTINVHDVETQFNQYKTEAASRYNLTISDVS
VSDVPFPFSAQSGAGVPGWGIALLVLVCVLVALAIVYLIALAVCQCRRKNYGQLDIFPAR
DTYHPMSEYPTYHTHGRYVPPSSTDRSPYEKVSAGNGGSSLSYTNPAVAATSANL

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Function
The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack.; The beta subunit contains a C-terminal domain which is involved in cell signaling, through phosphorylations and protein- protein interactions. Modulates signaling in ERK, SRC and NF-kappa-B pathways. In activated T-cells, influences directly or indirectly the Ras/MAPK pathway. Promotes tumor progression. Regulates TP53-mediated transcription and determines cell fate in the genotoxic stress response. Binds, together with KLF4, the PE21 promoter element of TP53 and represses TP53 activity.

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HGNC ID
HGNC:7508
KEGG ID hsa:4582
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
MUC1 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 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Lung injury ICD-11: NB32
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 MLE-12 cells Normal Mus musculus CVCL_3751
In Vivo Model
C57BL/6J male mice (6-8 weeks) were purchased from Slac Lab Animals (Shanghai, China). The basic principle of the CLP method was to find the caecum through anatomy and puncture at the blind end and extrude the contents into the abdominal cavity. Diffuse peritonitis was formed, and systemic infection appeared in mice. Mice in the control group were only treated with laparotomy.

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Response regulation Inhibition of MUC1 dimerization could increase the expression level of Keap1, reduce the phosphorylation level of GSK3, inhibit the entry of Nrf2 into the nucleus, further inhibit the expression level of GPX4, enhance the lipid peroxidation level of lung tissues, trigger ferroptosis, and aggravate lung injury. And inhibiting MUC1 reversed the alleviating effect of vitamin E on acute lung injury caused by sepsis.
Nuclear factor erythroid 2-related factor 2 (NFE2L2) [Suppressor; Marker]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Lung injury ICD-11: NB32
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 MLE-12 cells Normal Mus musculus CVCL_3751
In Vivo Model
C57BL/6J male mice (6-8 weeks) were purchased from Slac Lab Animals (Shanghai, China). The basic principle of the CLP method was to find the caecum through anatomy and puncture at the blind end and extrude the contents into the abdominal cavity. Diffuse peritonitis was formed, and systemic infection appeared in mice. Mice in the control group were only treated with laparotomy.

    Click to Show/Hide
Response regulation Inhibition of MUC1 dimerization could increase the expression level of Keap1, reduce the phosphorylation level of GSK3, inhibit the entry of Nrf2 into the nucleus, further inhibit the expression level of GPX4, enhance the lipid peroxidation level of lung tissues, trigger ferroptosis, and aggravate lung injury. And inhibiting MUC1 reversed the alleviating effect of vitamin E on acute lung injury caused by sepsis.
Cystine/glutamate transporter (SLC7A11) [Driver; Suppressor]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [2]
Target for Ferroptosis Suppressor
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 MDA-MB-468 cells Breast adenocarcinoma Homo sapiens CVCL_0419
MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
HEK-293T cells Normal Homo sapiens CVCL_0063
Response regulation MUC1-C binds directly with CD44v and in turn promotes stability of xCT (SLC7A11) in the cell membrane in breast adenocarcinoma. The interaction between 2MUC1-C and xCT is further supported by the demonstration that targeting xCT with silencing or the inhibitor sulfasalazine suppresses MUC1 gene transcription by increasing histone and DNA methylation on the MUC1 promoter.
Unspecific Target [Unspecific Target]
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [3]
Responsed Disease Oesophageal cancer ICD-11: 2B70
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 TE-1 cells Esophageal squamous cell carcinoma Homo sapiens CVCL_1759
KYSE30 cells Esophageal squamous cell carcinoma Homo sapiens CVCL_1351
In Vivo Model
A total of 128 immune active female C57BL/6 mice (6 weeks old) were procured from SLAC Laboratory Animal Co., Ltd. (Shanghai, China). ESCC cells (TE-1 and KYSE-30) resuspended in PBS were mixed with Matrigel and subcutaneously injected into the mice (1 x 106 cells per mouse) at the right flank to induce subcutaneous tumors. When the tumor size reached around 150 mm3, the tumor site was locally exposed to irradiation (2 Gy/d for consecutive 4 d). For antibody injection, the mice were injected with IgG or Anti-SIGECE on day 1, 7, or 14 after the first irradiation exposure. After 28 d, the mice were euthanized via overdosed barbiturate (150 mg/kg). The subcutaneous tumors were collected for IHC. Another group of ESCC cells were injected into mice via tail vein (2 x 106 cells per mouse).

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Response regulation LINC01004 recruited Spi-1 proto-oncogene (SPI1) in nucleus of TAMs to induce transcriptional activation of SIGLEC9. SIGLEC9 interacted with mucin 1 (MUC1). MUC1 overexpression in esophageal squamous cell carcinoma (ESCC) induced M2 skewing of TAMs, enhanced radioresistance and immunosuppression, and promoted nuclear translocation of -catenin to suppress radiotherapy-induced ferroptosis of ESCC cells.
Experiment 2 Reporting the Ferroptosis Target of This Regulator [4]
Responsed Disease Endometriosis ICD-11: GA10
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 hESCs (Human endometrial stromal cells)
In Vivo Model
Seven-to-8-week-old C57BL/6 female mice were obtained and 17-b-estradiol-3-benzoate (30 ug/kg, Sigma) was administered to each mouse every day for 3 days. We removed uterine horns from the donor mice and added them to saline. Endometrium was cut into 1 mm2 fragments. The endometrial fragments from each uterine horn were suspended in 0.3 ml saline and injected into the peritoneal cavities of recipient mice with an 18-gauge needle. At 8 days (5 days after the operation), endometrial-like lesions were established, and they were randomly divided into two groups (each group contained 12 mice). In the experimental group, each mouse received erastin (20 mg/kg/day) by intraperitoneal injection over a 7-day period. In the control group, DMSO was used instead of erastin.

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Response regulation Knockdown of MALAT1 facilitates erastin-induced ferroptosis by targeting miR-145-5p/ MUC1 signaling. The synergistic effect of MALAT1 knockdown and erastin induction in ferroptosis may be a new therapeutic strategy for endometriosis.
Breast cancer [ICD-11: 2C60]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Mucin-1 (MUC1) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 MDA-MB-468 cells Breast adenocarcinoma Homo sapiens CVCL_0419
MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
HEK-293T cells Normal Homo sapiens CVCL_0063
Response regulation MUC1-C binds directly with CD44v and in turn promotes stability of xCT (SLC7A11) in the cell membrane in breast adenocarcinoma. The interaction between 2MUC1-C and xCT is further supported by the demonstration that targeting xCT with silencing or the inhibitor sulfasalazine suppresses MUC1 gene transcription by increasing histone and DNA methylation on the MUC1 promoter.
Lung injury [ICD-11: NB32]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Mucin-1 (MUC1) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 MLE-12 cells Normal Mus musculus CVCL_3751
In Vivo Model
C57BL/6J male mice (6-8 weeks) were purchased from Slac Lab Animals (Shanghai, China). The basic principle of the CLP method was to find the caecum through anatomy and puncture at the blind end and extrude the contents into the abdominal cavity. Diffuse peritonitis was formed, and systemic infection appeared in mice. Mice in the control group were only treated with laparotomy.

    Click to Show/Hide
Response regulation Inhibition of MUC1 dimerization could increase the expression level of Keap1, reduce the phosphorylation level of GSK3, inhibit the entry of Nrf2 into the nucleus, further inhibit the expression level of GPX4, enhance the lipid peroxidation level of lung tissues, trigger ferroptosis, and aggravate lung injury. And inhibiting MUC1 reversed the alleviating effect of vitamin E on acute lung injury caused by sepsis.
Experiment 2 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Mucin-1 (MUC1) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 MLE-12 cells Normal Mus musculus CVCL_3751
In Vivo Model
C57BL/6J male mice (6-8 weeks) were purchased from Slac Lab Animals (Shanghai, China). The basic principle of the CLP method was to find the caecum through anatomy and puncture at the blind end and extrude the contents into the abdominal cavity. Diffuse peritonitis was formed, and systemic infection appeared in mice. Mice in the control group were only treated with laparotomy.

    Click to Show/Hide
Response regulation Inhibition of MUC1 dimerization could increase the expression level of Keap1, reduce the phosphorylation level of GSK3, inhibit the entry of Nrf2 into the nucleus, further inhibit the expression level of GPX4, enhance the lipid peroxidation level of lung tissues, trigger ferroptosis, and aggravate lung injury. And inhibiting MUC1 reversed the alleviating effect of vitamin E on acute lung injury caused by sepsis.
Oesophageal cancer [ICD-11: 2B70]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [3]
Target Regulator Mucin-1 (MUC1) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 TE-1 cells Esophageal squamous cell carcinoma Homo sapiens CVCL_1759
KYSE30 cells Esophageal squamous cell carcinoma Homo sapiens CVCL_1351
In Vivo Model
A total of 128 immune active female C57BL/6 mice (6 weeks old) were procured from SLAC Laboratory Animal Co., Ltd. (Shanghai, China). ESCC cells (TE-1 and KYSE-30) resuspended in PBS were mixed with Matrigel and subcutaneously injected into the mice (1 x 106 cells per mouse) at the right flank to induce subcutaneous tumors. When the tumor size reached around 150 mm3, the tumor site was locally exposed to irradiation (2 Gy/d for consecutive 4 d). For antibody injection, the mice were injected with IgG or Anti-SIGECE on day 1, 7, or 14 after the first irradiation exposure. After 28 d, the mice were euthanized via overdosed barbiturate (150 mg/kg). The subcutaneous tumors were collected for IHC. Another group of ESCC cells were injected into mice via tail vein (2 x 106 cells per mouse).

    Click to Show/Hide
Response regulation LINC01004 recruited Spi-1 proto-oncogene (SPI1) in nucleus of TAMs to induce transcriptional activation of SIGLEC9. SIGLEC9 interacted with mucin 1 (MUC1). MUC1 overexpression in esophageal squamous cell carcinoma (ESCC) induced M2 skewing of TAMs, enhanced radioresistance and immunosuppression, and promoted nuclear translocation of -catenin to suppress radiotherapy-induced ferroptosis of ESCC cells.
Endometriosis [ICD-11: GA10]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [4]
Target Regulator Mucin-1 (MUC1) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 hESCs (Human endometrial stromal cells)
In Vivo Model
Seven-to-8-week-old C57BL/6 female mice were obtained and 17-b-estradiol-3-benzoate (30 ug/kg, Sigma) was administered to each mouse every day for 3 days. We removed uterine horns from the donor mice and added them to saline. Endometrium was cut into 1 mm2 fragments. The endometrial fragments from each uterine horn were suspended in 0.3 ml saline and injected into the peritoneal cavities of recipient mice with an 18-gauge needle. At 8 days (5 days after the operation), endometrial-like lesions were established, and they were randomly divided into two groups (each group contained 12 mice). In the experimental group, each mouse received erastin (20 mg/kg/day) by intraperitoneal injection over a 7-day period. In the control group, DMSO was used instead of erastin.

    Click to Show/Hide
Response regulation Knockdown of MALAT1 facilitates erastin-induced ferroptosis by targeting miR-145-5p/ MUC1 signaling. The synergistic effect of MALAT1 knockdown and erastin induction in ferroptosis may be a new therapeutic strategy for endometriosis.
References
Ref 1 Mucin 1 Inhibits Ferroptosis and Sensitizes Vitamin E to Alleviate Sepsis-Induced Acute Lung Injury through GSK3/Keap1-Nrf2-GPX4 Pathway. Oxid Med Cell Longev. 2022 Jul 21;2022:2405943. doi: 10.1155/2022/2405943. eCollection 2022.
Ref 2 Functional interactions of the cystine/glutamate antiporter, CD44v and MUC1-C oncoprotein in triple-negative breast cancer cells. Oncotarget. 2016 Mar 15;7(11):11756-69. doi: 10.18632/oncotarget.7598.
Ref 3 LINC01004-SPI1 axis-activated SIGLEC9 in tumor-associated macrophages induces radioresistance and the formation of immunosuppressive tumor microenvironment in esophageal squamous cell carcinoma. Cancer Immunol Immunother. 2023 Jun;72(6):1835-1851. doi: 10.1007/s00262-022-03364-5. Epub 2023 Jan 23.
Ref 4 Silencing of lncRNA MALAT1 facilitates erastin-induced ferroptosis in endometriosis through miR-145-5p/MUC1 signaling. Cell Death Discov. 2022 Apr 11;8(1):190. doi: 10.1038/s41420-022-00975-w.