Ferroptosis-centered Disease Response Information

General Information of the Disease (ID: DIS00032)

Name	Gallbladder cancer
ICD	ICD-11: 2C13

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

Nuclear factor erythroid 2-related factor 2 (NFE2L2)

Target Info

In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target				[1]
Target for Ferroptosis	Marker/Suppressor
Responsed Disease	Gallbladder cancer [ICD-11: 2C13]
Responsed Regulator	Transcription factor AP-2-alpha (TFAP2A)		Suppressor	Regulator Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell migration
	Cell invasion
In Vitro Model	H69 cells	Normal	Homo sapiens	CVCL_8121
	GBC-SD cells	Gallbladder carcinoma	Homo sapiens	CVCL_6903
Response regulation	In vitro, gallbladder carcinoma (GBC) exhibited upregulated expression of TFAP2A, whose inhibition reduced GBC cell proliferation, migration, and invasion. Fe2+ and MDA levels were elevated. TFAP2A silencing attenuated the expression of key genes associated with oxidative stress such as heme oxygenase 1 (HO-1), nuclear factor erythroid 2 like 2 (Nrf2), ferritin heavy chain 1 (FTH1) and NAD(P)H quinone dehydrogenase 1 (NQO1).

NAD(P)H dehydrogenase [quinone] 1 (NQO1)

Target Info

In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target				[1]
Target for Ferroptosis	Suppressor
Responsed Disease	Gallbladder cancer [ICD-11: 2C13]
Responsed Regulator	Transcription factor AP-2-alpha (TFAP2A)		Suppressor	Regulator Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell migration
	Cell invasion
In Vitro Model	H69 cells	Normal	Homo sapiens	CVCL_8121
	GBC-SD cells	Gallbladder carcinoma	Homo sapiens	CVCL_6903
Response regulation	In vitro, gallbladder carcinoma (GBC) exhibited upregulated expression of TFAP2A, whose inhibition reduced GBC cell proliferation, migration, and invasion. Fe2+ and MDA levels were elevated. TFAP2A silencing attenuated the expression of key genes associated with oxidative stress such as heme oxygenase 1 (HO-1), nuclear factor erythroid 2 like 2 (Nrf2), ferritin heavy chain 1 (FTH1) and NAD(P)H quinone dehydrogenase 1 (NQO1).

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

Target Info

In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target				[2]
Target for Ferroptosis	Driver
Responsed Disease	Gallbladder cancer [ICD-11: 2C13]
Responsed Regulator	NAD-dependent protein deacetylase sirtuin-3, mitochondrial (SIRT3)		Driver	Regulator Info
Pathway Response	Ferroptosis			hsa04216
	Cell adhesion molecules			hsa04514
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell migration
	Cell invasion
In Vitro Model	GBC-SD cells	Gallbladder carcinoma	Homo sapiens	CVCL_6903
	EH-GB1 cells	Gallbladder carcinoma	Homo sapiens	CVCL_IU73
	OCUG-1 cells	Gallbladder carcinoma	Homo sapiens	CVCL_3083
	NOZ cells	Gallbladder carcinoma	Homo sapiens	CVCL_3079
In Vivo Model	Forty male BALB/cnude mice (4 weeks old, 15-16 g) were purchased from the Shanghai Laboratory Animal Center (Shanghai, China) and divided into eight groups. Cells (1.0 x 10⁶) were subcutaneously injected into the leftaxillaof nude mice. Click to Show/Hide
Response regulation	Expression levels of SIRT3 in patients with gallbladder cancer were lower than those in the adjacent normal tissue. Silence of SIRT3 gene also suppressed AKT-dependent ferroptosis, an iron-dependent and lipid peroxide-mediated cell death. Blockade of AKT activity in sh-SIRT3 cells induced ACSL4 expression that drives ferroptosis, and inhibited epithelial-mesenchymal (EMT) markers and invasive activity.

Heme oxygenase 1 (HMOX1)

Target Info

In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target				[1]
Target for Ferroptosis	Driver/Suppressor
Responsed Disease	Gallbladder cancer [ICD-11: 2C13]
Responsed Regulator	Transcription factor AP-2-alpha (TFAP2A)		Suppressor	Regulator Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell migration
	Cell invasion
In Vitro Model	H69 cells	Normal	Homo sapiens	CVCL_8121
	GBC-SD cells	Gallbladder carcinoma	Homo sapiens	CVCL_6903
Response regulation	In vitro, gallbladder carcinoma (GBC) exhibited upregulated expression of TFAP2A, whose inhibition reduced GBC cell proliferation, migration, and invasion. Fe2+ and MDA levels were elevated. TFAP2A silencing attenuated the expression of key genes associated with oxidative stress such as heme oxygenase 1 (HO-1), nuclear factor erythroid 2 like 2 (Nrf2), ferritin heavy chain 1 (FTH1) and NAD(P)H quinone dehydrogenase 1 (NQO1).

Ferritin heavy chain (FTH1)

Target Info

In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target				[1]
Target for Ferroptosis	Marker/Suppressor
Responsed Disease	Gallbladder cancer [ICD-11: 2C13]
Responsed Regulator	Transcription factor AP-2-alpha (TFAP2A)		Suppressor	Regulator Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell migration
	Cell invasion
In Vitro Model	H69 cells	Normal	Homo sapiens	CVCL_8121
	GBC-SD cells	Gallbladder carcinoma	Homo sapiens	CVCL_6903
Response regulation	In vitro, gallbladder carcinoma (GBC) exhibited upregulated expression of TFAP2A, whose inhibition reduced GBC cell proliferation, migration, and invasion. Fe2+ and MDA levels were elevated. TFAP2A silencing attenuated the expression of key genes associated with oxidative stress such as heme oxygenase 1 (HO-1), nuclear factor erythroid 2 like 2 (Nrf2), ferritin heavy chain 1 (FTH1) and NAD(P)H quinone dehydrogenase 1 (NQO1).

References

Ref 1	TFAP2A is a novel regulator that modulates ferroptosis in gallbladder carcinoma cells via the Nrf2 signalling axis. Eur Rev Med Pharmacol Sci. 2020 May;24(9):4745-4755. doi: 10.26355/eurrev_202005_21163.
Ref 2	SIRT3 inhibits gallbladder cancer by induction of AKT-dependent ferroptosis and blockade of epithelial-mesenchymal transition. Cancer Lett. 2021 Jul 10;510:93-104. doi: 10.1016/j.canlet.2021.04.007. Epub 2021 Apr 16.