Ferroptosis-centered Disease Response Information

General Information of the Disease (ID: DIS00128)

Name	Primary ovarian insufficiency
ICD	ICD-11: GA30

Full List of Target(s) of This Ferroptosis-centered Disease

Transferrin receptor protein 1 (TFRC)

Target Info

In total 3 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target				[1]
Target for Ferroptosis	Marker/Suppressor/Driver
Responsed Disease	Primary ovarian insufficiency [ICD-11: GA30]
Responsed Regulator	Transcriptional coactivator YAP1 (YAP1)		Driver	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 by This Target				[1]
Target for Ferroptosis	Marker/Suppressor/Driver
Responsed Disease	Primary ovarian insufficiency [ICD-11: GA30]
Responsed Regulator	Zinc finger protein basonuclin-1 (BNC1)		Suppressor	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 Bnc 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 3 Reporting the Ferroptosis-centered Disease Response by This Target				[1]
Target for Ferroptosis	Marker/Suppressor/Driver
Responsed Disease	Primary ovarian insufficiency [ICD-11: GA30]
Responsed Regulator	Merlin (NF2)		Suppressor	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.

Long-chain-fatty-acid--CoA ligase 4 (ACSL4)

Target Info

In total 3 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target				[1]
Target for Ferroptosis	Driver
Responsed Disease	Primary ovarian insufficiency [ICD-11: GA30]
Responsed Regulator	Transcriptional coactivator YAP1 (YAP1)		Driver	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 by This Target				[1]
Target for Ferroptosis	Driver
Responsed Disease	Primary ovarian insufficiency [ICD-11: GA30]
Responsed Regulator	Zinc finger protein basonuclin-1 (BNC1)		Suppressor	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 Bnc 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 3 Reporting the Ferroptosis-centered Disease Response by This Target				[1]
Target for Ferroptosis	Driver
Responsed Disease	Primary ovarian insufficiency [ICD-11: GA30]
Responsed Regulator	Merlin (NF2)		Suppressor	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.

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.

Ferroptosis-centered Disease Response Information

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Correspondence

Prof. Shuiping Liu