Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10138)
Regulator Name Merlin (NF2)
Synonyms
SCH; Moesin-ezrin-radixin-like protein; Neurofibromin-2; Schwannomerlin; Schwannomin
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Gene Name NF2
Gene ID 4771
Regulator Type Protein coding
Uniprot ID P35240
Sequence
MAGAIASRMSFSSLKRKQPKTFTVRIVTMDAEMEFNCEMKWKGKDLFDLVCRTLGLRETW
FFGLQYTIKDTVAWLKMDKKVLDHDVSKEEPVTFHFLAKFYPENAEEELVQEITQHLFFL
QVKKQILDEKIYCPPEASVLLASYAVQAKYGDYDPSVHKRGFLAQEELLPKRVINLYQMT
PEMWEERITAWYAEHRGRARDEAEMEYLKIAQDLEMYGVNYFAIRNKKGTELLLGVDALG
LHIYDPENRLTPKISFPWNEIRNISYSDKEFTIKPLDKKIDVFKFNSSKLRVNKLILQLC
IGNHDLFMRRRKADSLEVQQMKAQAREEKARKQMERQRLAREKQMREEAERTRDELERRL
LQMKEEATMANEALMRSEETADLLAEKAQITEEEAKLLAQKAAEAEQEMQRIKATAIRTE
EEKRLMEQKVLEAEVLALKMAEESERRAKEADQLKQDLQEAREAERRAKQKLLEIATKPT
YPPMNPIPAPLPPDIPSFNLIGDSLSFDFKDTDMKRLSMEIEKEKVEYMEKSKHLQEQLN
ELKTEIEALKLKERETALDILHNENSDRGGSSKHNTIKKLTLQSAKSRVAFFEEL

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Function
Probable regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, a signaling pathway that plays a pivotal role in tumor suppression by restricting proliferation and promoting apoptosis. Along with WWC1 can synergistically induce the phosphorylation of LATS1 and LATS2 and can probably function in the regulation of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway. May act as a membrane stabilizing protein. May inhibit PI3 kinase by binding to AGAP2 and impairing its stimulating activity. Suppresses cell proliferation and tumorigenesis by inhibiting the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase complex.

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HGNC ID
HGNC:7773
KEGG ID hsa:4771
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
NF2 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
Transferrin receptor protein 1 (TFRC) [Driver; 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/Driver
Responsed Disease Primary ovarian insufficiency ICD-11: GA30
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Hippo signaling pathway hsa04390
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 ES-2 cells Ovarian clear cell adenocarcinoma Homo sapiens CVCL_3509
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
Ovaries collected from 12-week-old mice were fixed in 2.5% glutaraldehyde at room temperature for 2 h and then at 4 overnight. The ovaries were washed with PBS three times for 10 min. Then, the ovaries were fixed with 1% osmic acid for 1 h and washed with PBS three times for 10 min each. The ovaries were fixed with 2% uranyl acetate for 30 min; dehydrated with 50%, 70%, 90% and 100% ethanol for 10 min each; and washed with 100% acetone twice for 15 min each.

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Response regulation Pharmacologic inhibition of YAP signaling or ferroptosis significantly rescues Bnc1 mutation-induced primary ovarian insufficiency (POI). BNC1 directly regulates Nf2 expression. BNC1 deficiency downregulates NF2 expression, which reduces YAP phosphorylation and promote YAP nuclear accumulation. YAP activation upregulates Tfrc and Acsl4 expression.
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 Primary ovarian insufficiency ICD-11: GA30
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Hippo signaling pathway hsa04390
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 ES-2 cells Ovarian clear cell adenocarcinoma Homo sapiens CVCL_3509
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
Ovaries collected from 12-week-old mice were fixed in 2.5% glutaraldehyde at room temperature for 2 h and then at 4 overnight. The ovaries were washed with PBS three times for 10 min. Then, the ovaries were fixed with 1% osmic acid for 1 h and washed with PBS three times for 10 min each. The ovaries were fixed with 2% uranyl acetate for 30 min; dehydrated with 50%, 70%, 90% and 100% ethanol for 10 min each; and washed with 100% acetone twice for 15 min each.

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Response regulation Pharmacologic inhibition of YAP signaling or ferroptosis significantly rescues Bnc1 mutation-induced primary ovarian insufficiency (POI). BNC1 directly regulates Nf2 expression. BNC1 deficiency downregulates NF2 expression, which reduces YAP phosphorylation and promote YAP nuclear accumulation. YAP activation upregulates Tfrc and Acsl4 expression.
Ferroptosis suppressor protein 1 (AIFM2) [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
Cell proliferation
In Vitro Model
 hMPs (Human macrophages)
In Vivo Model
C57BL/6 mice (female, 6-8 weeks old, 20-30 g weight) and SPF-grade SD rats (female, 180-230 g weight) were used to detect the toxicity of nanoparticles. Different cells (5 x 106) cells were grafted in the left flank; 5 days after engraftation, the stimulated TAMs (1 x 106) were injected into NSG mice through the tail vein. Different treatments were given and recorded as day 0.

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Response regulation The NF2-YAP signaling axis modulated the expression of ferroptosis suppressor protein 1 (FSP1) and CD24 in CD24 high cells. This system achieved dual antitumor effects, ultimately promoting cell death and thus inhibiting triple-negative breast cancer (TNBC) tumor growth, with some tumors even disappearing.
Unspecific Target [Unspecific Target]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [3]
Responsed Disease Meningiomas ICD-11: 2A01
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 CH-157MN cells Meningioma Homo sapiens CVCL_5723
IOMM-Lee cells Intracranial meningioma Homo sapiens CVCL_5779
PM3 (Human meningioma cells)
In Vivo Model
6-week-old male nude mice (Nanjing Medical University Animal Center) were used in this study. There were 6-8 mice/group for survival and tumor growth analysis experiments. For tumor growth analysis, (2 x 106) IOMM-Lee-shMEF2C, IOMM-Lee-shMEF2C-Lv-NF2 or IOMM-Lee-shMEF2C-Lv-Ecad cells were subcutaneously injected to the right flank of the mice to examine the effect of MEF2C, NF2 and E-cadherin status on ferropotosis inducing response in vivo. Erastin, 15 mg/kg in 10% DMSO, or vehicle was administrated intraperitoneally (i.p.) every other day starting at Day 5 after implantation. Tumor diameter was recorded every 5 days starting at Day 10 when the tumors were visible and detectable.

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Response regulation MEF2C was found to drive the expression of both NF2 and E-cadherin. NF2 loss and low CDH1 (E-cadherin) create susceptibility to ferroptosis in meningioma. MEF2C could be a new molecular target in ferroptosis-inducing therapies for meningioma.
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 Merlin (NF2) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 hMPs (Human macrophages)
In Vivo Model
C57BL/6 mice (female, 6-8 weeks old, 20-30 g weight) and SPF-grade SD rats (female, 180-230 g weight) were used to detect the toxicity of nanoparticles. Different cells (5 x 106) cells were grafted in the left flank; 5 days after engraftation, the stimulated TAMs (1 x 106) were injected into NSG mice through the tail vein. Different treatments were given and recorded as day 0.

    Click to Show/Hide
Response regulation The NF2-YAP signaling axis modulated the expression of ferroptosis suppressor protein 1 (FSP1) and CD24 in CD24 high cells. This system achieved dual antitumor effects, ultimately promoting cell death and thus inhibiting triple-negative breast cancer (TNBC) tumor growth, with some tumors even disappearing.
Primary ovarian insufficiency [ICD-11: GA30]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Merlin (NF2) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Hippo signaling pathway hsa04390
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 ES-2 cells Ovarian clear cell adenocarcinoma Homo sapiens CVCL_3509
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
Ovaries collected from 12-week-old mice were fixed in 2.5% glutaraldehyde at room temperature for 2 h and then at 4 overnight. The ovaries were washed with PBS three times for 10 min. Then, the ovaries were fixed with 1% osmic acid for 1 h and washed with PBS three times for 10 min each. The ovaries were fixed with 2% uranyl acetate for 30 min; dehydrated with 50%, 70%, 90% and 100% ethanol for 10 min each; and washed with 100% acetone twice for 15 min each.

    Click to Show/Hide
Response regulation Pharmacologic inhibition of YAP signaling or ferroptosis significantly rescues Bnc1 mutation-induced primary ovarian insufficiency (POI). BNC1 directly regulates Nf2 expression. BNC1 deficiency downregulates NF2 expression, which reduces YAP phosphorylation and promote YAP nuclear accumulation. YAP activation upregulates Tfrc and Acsl4 expression.
Experiment 2 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Merlin (NF2) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Hippo signaling pathway hsa04390
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 ES-2 cells Ovarian clear cell adenocarcinoma Homo sapiens CVCL_3509
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
Ovaries collected from 12-week-old mice were fixed in 2.5% glutaraldehyde at room temperature for 2 h and then at 4 overnight. The ovaries were washed with PBS three times for 10 min. Then, the ovaries were fixed with 1% osmic acid for 1 h and washed with PBS three times for 10 min each. The ovaries were fixed with 2% uranyl acetate for 30 min; dehydrated with 50%, 70%, 90% and 100% ethanol for 10 min each; and washed with 100% acetone twice for 15 min each.

    Click to Show/Hide
Response regulation Pharmacologic inhibition of YAP signaling or ferroptosis significantly rescues Bnc1 mutation-induced primary ovarian insufficiency (POI). BNC1 directly regulates Nf2 expression. BNC1 deficiency downregulates NF2 expression, which reduces YAP phosphorylation and promote YAP nuclear accumulation. YAP activation upregulates Tfrc and Acsl4 expression.
Meningiomas [ICD-11: 2A01]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [3]
Target Regulator Merlin (NF2) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 CH-157MN cells Meningioma Homo sapiens CVCL_5723
IOMM-Lee cells Intracranial meningioma Homo sapiens CVCL_5779
PM3 (Human meningioma cells)
In Vivo Model
6-week-old male nude mice (Nanjing Medical University Animal Center) were used in this study. There were 6-8 mice/group for survival and tumor growth analysis experiments. For tumor growth analysis, (2 x 106) IOMM-Lee-shMEF2C, IOMM-Lee-shMEF2C-Lv-NF2 or IOMM-Lee-shMEF2C-Lv-Ecad cells were subcutaneously injected to the right flank of the mice to examine the effect of MEF2C, NF2 and E-cadherin status on ferropotosis inducing response in vivo. Erastin, 15 mg/kg in 10% DMSO, or vehicle was administrated intraperitoneally (i.p.) every other day starting at Day 5 after implantation. Tumor diameter was recorded every 5 days starting at Day 10 when the tumors were visible and detectable.

    Click to Show/Hide
Response regulation MEF2C was found to drive the expression of both NF2 and E-cadherin. NF2 loss and low CDH1 (E-cadherin) create susceptibility to ferroptosis in meningioma. MEF2C could be a new molecular target in ferroptosis-inducing therapies for meningioma.
References
Ref 1 BNC1 deficiency-triggered ferroptosis through the NF2-YAP pathway induces primary ovarian insufficiency. Nat Commun. 2022 Oct 5;13(1):5871. doi: 10.1038/s41467-022-33323-8.
Ref 2 Targeted Intervention of NF2-YAP Signaling Axis in CD24-Overexpressing Cells Contributes to Encouraging Therapeutic Effects in TNBC. ACS Nano. 2022 Apr 26;16(4):5807-5819. doi: 10.1021/acsnano.1c10921. Epub 2022 Apr 14.
Ref 3 MEF2C silencing downregulates NF2 and E-cadherin and enhances Erastin-induced ferroptosis in meningioma. Neuro Oncol. 2021 Dec 1;23(12):2014-2027. doi: 10.1093/neuonc/noab114.