Ferroptosis Target Information

General Information of the Ferroptosis Target (ID: TAR10052)

Target Name	4F2 cell-surface antigen heavy chain (SLC3A2)
Synonyms	4F2 heavy chain antigen ; Lymphocyte activation antigen 4F2 large subunit ; Solute carrier family 3 member 2 ; CD_antigen=CD98 Click to Show/Hide
Gene Name	SLC3A2
Sequence	MELQPPEASIAVVSIPRQLPGSHSEAGVQGLSAGDDSELGSHCVAQTGLELLASGDPLPS ASQNAEMIETGSDCVTQAGLQLLASSDPPALASKNAEVTGTMSQDTEVDMKEVELNELEP EKQPMNAASGAAMSLAGAEKNGLVKIKVAEDEAEAAAAAKFTGLSKEELLKVAGSPGWVR TRWALLLLFWLGWLGMLAGAVVIIVRAPRCRELPAQKWWHTGALYRIGDLQAFQGHGAGN LAGLKGRLDYLSSLKVKGLVLGPIHKNQKDDVAQTDLLQIDPNFGSKEDFDSLLQSAKKK SIRVILDLTPNYRGENSWFSTQVDTVATKVKDALEFWLQAGVDGFQVRDIENLKDASSFL AEWQNITKGFSEDRLLIAGTNSSDLQQILSLLESNKDLLLTSSYLSDSGSTGEHTKSLVT QYLNATGNRWCSWSLSQARLLTSFLPAQLLRLYQLMLFTLPGTPVFSYGDEIGLDAAALP GQPMEAPVMLWDESSFPDIPGAVSANMTVKGQSEDPGSLLSLFRRLSDQRSKERSLLHGD FHAFSAGPGLFSYIRHWDQNERFLVVLNFGDVGLSAGLQASDLPASASLPAKADLLLSTQ PGREEGSPLELERLKLEPHEGLLLRFPYAA Click to Show/Hide
Family	SLC3A transporter family
Function	Component of several heterodimeric complexes involved in amino acid transport. The precise substrate specificity depends on the other subunit in the heterodimer. The complexes function as amino acid exchangers. The heterodimer functions as sodium-independent, high-affinity transporter that mediates uptake of large neutral amino acids such as phenylalanine, tyrosine, leucine, histidine, methionine, tryptophan, valine and isoleucine. The heterodimer with SLC7A5/LAT1 mediates the uptake of L-DOPA. The heterodimer formed by SLC3A2 and SLC7A6 or SLC3A2 and SLC7A7 mediates the uptake of dibasic amino acids . The heterodimer with SLC7A5/LAT1 mediates the transport of thyroid hormones diiodothyronine (T2), triiodothyronine (T3) and thyroxine (T4) across the cell membrane . The heterodimer with SLC7A5/LAT1 is involved in the uptake of toxic methylmercury (MeHg) when administered as the L-cysteine or D,L-homocysteine complexes. When associated with LAPTM4B, the heterodimer with SLC7A5/LAT1 is recruited to lysosomes to promote leucine uptake into these organelles, and thereby mediates mTORC1 activation. The heterodimer with SLC7A5/LAT1 may play a role in the transport of L-DOPA across the blood-brain barrier. The heterodimer formed by SLC3A2 and SLC7A5/LAT1 or SLC3A2 and SLC7A8/LAT2 is involved in the cellular activity of small molecular weight nitrosothiols, via the stereoselective transport of L- nitrosocysteine (L-CNSO) across the transmembrane. The heterodimer with SLC7A10 translocates small neutral L- and D-amino acids across the plasma membrane. SLC3A2-SLC7A10 preferentially mediates exchange transport, but can also operate via facilitated diffusion. Together with ICAM1, regulates the transport activity of SLC7A8/LAT2 in polarized intestinal cells by generating and delivering intracellular signals. Required for targeting of SLC7A5/LAT1 and SLC7A8/LAT2 to the plasma membrane and for channel activity. Plays a role in nitric oxide synthesis in human umbilical vein endothelial cells (HUVECs) via transport of L-arginine. May mediate blood-to-retina L-leucine transport across the inner blood-retinal barrier. Click to Show/Hide
Gene ID	6520
Uniprot ID	P08195
Target Type	Driver Suppressor Marker
Mechanism Diagram	Click to View the Original Diagram

Tissue Relative Abundances of This Target

Full List of Regulator(s) of This Ferroptosis Target and Corresponding Disease/Drug Response(s)

SLC3A2 can be involved in and affect the ferroptosis by the following regulators, and result in corresponding disease/drug response(s). You can browse corresponding disease or drug response(s) resulting from the regulation of certain regulators.

Browse Regulator related Disease

Browse Regulator related Drug

Neutrophil gelatinase-associated lipocalin (LCN2)

Regulator Info

Intracerebral hemorrhage [ICD-11: 8B00]

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator			[1]
Regulator for Ferroptosis	Driver
Responsed Drug	Dihydromyricetin	Investigative	Drug Info
Pathway Response	Fatty acid metabolism		hsa01212
	Ferroptosis		hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	hBCs (Brain cells)
In Vivo Model	Male C57BL/6 mice, aged 8-10 weeks and weighing 22-25 g, were purchased from the Hubei Provincial Center for Disease Control and Prevention in Wuhan, China. Mice were initially administered with 1% sodium pentobarbital (70 mg/kg; Sinopharm Chemical Agent Co., Ltd., Shanghai, China) intraperitoneally. Subsequently, they were secured on a stereotaxic device (RWD Life Science Co., Shenzhen). 0.6 ul of collagenase (1 ku/ml) was injected into the caudate nucleus of the mice (bregma 0: 0.5 mm anterior, 2 mm left lateral and 3.5 mm deep) with the help of a brain stereotactic sampling needle (Hamilton). Click to Show/Hide
Response Description	Dihydromyricetin (DMY) may attenuate symptoms of intracerebral hemorrhage (ICH) in mice, and its potential mechanisms are closely linked to LCN2/system Xc-. The ICH-induced augmentation of LCN2 expression leads to the formation of LCN2-SLC3A2 complexes, which suppress the transport activity of system Xc- and result in the accumulation of ROS and the emergence of ferroptosis.

Bromodomain-containing protein 4 (BRD4)

Regulator Info

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[2]
Regulator for Ferroptosis	Suppressor
Responsed Drug	JQ1		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Apoptosis			hsa04210
	Autophagy			hsa04140
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell autophagy
	Cell proliferation
	Cell migration
	Cell invasion
In Vitro Model	MDA-MB-231 cells	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	Hs-578T cells	Invasive breast carcinoma	Homo sapiens	CVCL_0332
	NCI-H1299 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	MCF-10A cells	Normal	Homo sapiens	CVCL_0598
In Vivo Model	Female athymic BALB/c nude mice (4-6-week old) were obtained from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). Approximately 1 x 10⁷ cells (A549) in 200 uL of serum-free medium and Matrigel solution were injected directly into the right axilla of each mouse. Tumor growth was measured with calipers every 3 days. Click to Show/Hide
Response Description	Ferroptosis was induced under (+)-JQ1 treatment and BRD4 knockdown, indicating that (+)-JQ1 induces ferroptosis via BRD4 inhibition in breast adenocarcinoma. In addition, expression of the ferroptosis-associated genes GPX4, SLC7A11, and SLC3A2 was downregulated under (+)-JQ1 treatment. Moreover, JQ1 treatment and BRD4 knockdown led to decreased FTH1 expression.

Protein LYRIC (MTDH)

Regulator Info

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[3]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
Cell Process	Cell proliferation
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H1975 cells	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	DMS53 cells	Lung small cell carcinoma	Homo sapiens	CVCL_1177
	DMS 273 cells	Lung small cell carcinoma	Homo sapiens	CVCL_1176
	KLE cells	Endometrial adenocarcinoma	Homo sapiens	CVCL_1329
	AN3CA cells	Endometrial adenocarcinoma	Homo sapiens	CVCL_0028
	RL95-2 cells	Endometrial adenosquamous carcinoma	Homo sapiens	CVCL_0505
	HEC-1-A cells	Endometrial adenocarcinoma	Homo sapiens	CVCL_0293
	Ishikawa cells	Endometrial adenocarcinoma	Homo sapiens	CVCL_2529
	MDA-MB-231 cells	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MCF-7 cells	Breast carcinoma	Homo sapiens	CVCL_0031
	Hec50 cells	Endometrial adenocarcinoma	Homo sapiens	CVCL_2929
In Vivo Model	To generate tumor xenograft models, 5 x 10⁶ MTDH WT and KO MDA-MB-231 cells were injected into the second and fifth mammary fat pads (both sides, total four sites) of the NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG, Jackson Laboratories, Bar Harbor, ME) immunodeficient female mice. To study the metastasis from this orthotopic mouse model, tumor volumes were allowed to grow to ~1000 mm³, after which livers were resected to examine incidence as well as tumor burden of liver metastasis. Click to Show/Hide
Response Description	Metadherin (MTDH) confers a therapy-resistant mesenchymal-high cell state and enhanced sensitivity to inducers of ferroptosis. Mechanistically, MTDH inhibited GPx4, as well as the solute carrier family 3 member 2 (SLC3A2, a system Xc-heterodimerization partner), at both the messenger RNA and protein levels in Lung adenocarcinoma.

Interferon gamma (IFNG)

Regulator Info

Fibrosarcoma [ICD-11: 2B53]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[4]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	HT-1080 cells	Fibrosarcoma	Homo sapiens	CVCL_0317
	A-375 cells	Amelanotic melanoma	Homo sapiens	CVCL_0132
	B16-F0 cells	Melanoma	Mus musculus	CVCL_0604
	ID8 cells	Ovarian cancer	Mus musculus	CVCL_IU14
In Vivo Model	Six- to eight-week-old female NSG or C57BL/6 mice were obtained from the Jackson Laboratory. For HT-1080 tumor model, 10⁶ tumor cells were subcutaneously injected on the right flank of NSG mice. For adoptive transfer of OT-I to B16-OVA model, 105 B16-OVA cells were subcutaneously injected on the right flank of C57BL/6 mice. For the B16 tumor model, 105 B16F0 cells were subcutaneously injected on the right flank of C57BL/6 mice. For the ID8 tumor model, 2 x 10⁶ luciferase-expressing ID8 cells were injected into the peritoneal cavity of each female mouse. Click to Show/Hide
Response Description	Interferon gamma (IFNG) released from CD8T cells downregulates the expression of SLC3A2 and SLC7A11, two subunits of the glutamate-cystine antiporter system xc-, impairs the uptake of cystine by tumour cells, and as a consequence, promotes tumour cell lipid peroxidation and ferroptosis in Fibrosarcoma.

hsa-miR-372-3p (miRNA)

Regulator Info

Oesophageal cancer [ICD-11: 2B70]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[5]
Regulator for Ferroptosis	Suppressor
Pathway Response	Glutathione metabolism			hsa00480
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell migration
In Vitro Model	EC9706 cells	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_E307
	TE-1 cells	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1759
	Eca-109 cells	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_6898
	HET-1A cells	Normal	Homo sapiens	CVCL_3702
Response Description	ARHGEF26-AS1 facilitated ferroptosis but restrained cell growth and positively regulated ADAM23 by sponging miR-372-3p in esophageal squamous cell carcinoma (ESCC). Overexpression of ARHGEF26-AS1 upregulated the protein levels of ADAM23 but depleted the protein levels of GPX4, SLC3A2, and SLC7A11.

hsa-miR-142-3p (miRNA)

Regulator Info

Hepatocellular carcinoma [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[6]
Regulator for Ferroptosis	Driver
Pathway Response	Glutathione metabolism			hsa00480
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell migration
	Cell invasion
In Vitro Model	Hep-G2 cells	Hepatoblastoma	Homo sapiens	CVCL_0027
	THP-1 cells	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
Response Description	MiR-142-3p promoted HBV-infected M1-type macrophage ferroptosis through SLC3A2, affecting the production of GSH, MDA, and Fe2+and accelerating the development of hepatocellular carcinoma (HCC). Inhibition of miR-142-3p or overexpression of SLC3A2 reversed ferroptosis and inhibited the proliferation, migration, and invasion of HCC cells.

Disintegrin and metalloproteinase domain-containing protein 23 (ADAM23)

Regulator Info

Oesophageal cancer [ICD-11: 2B70]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[5]
Regulator for Ferroptosis	Driver
Pathway Response	Glutathione metabolism			hsa00480
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell migration
In Vitro Model	EC9706 cells	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_E307
	TE-1 cells	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1759
	Eca-109 cells	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_6898
	HET-1A cells	Normal	Homo sapiens	CVCL_3702
Response Description	ARHGEF26-AS1 facilitated ferroptosis but restrained cell growth and positively regulated ADAM23 by sponging miR-372-3p in esophageal squamous cell carcinoma (ESCC). Overexpression of ARHGEF26-AS1 upregulated the protein levels of ADAM23 but depleted the protein levels of GPX4, SLC3A2, and SLC7A11.

ARHGEF26-AS1 (IncRNA)

Regulator Info

Oesophageal cancer [ICD-11: 2B70]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[5]
Regulator for Ferroptosis	Driver
Pathway Response	Glutathione metabolism			hsa00480
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell migration
In Vitro Model	EC9706 cells	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_E307
	TE-1 cells	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1759
	Eca-109 cells	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_6898
	HET-1A cells	Normal	Homo sapiens	CVCL_3702
Response Description	ARHGEF26-AS1 facilitated ferroptosis but restrained cell growth and positively regulated ADAM23 by sponging miR-372-3p in esophageal squamous cell carcinoma (ESCC). Overexpression of ARHGEF26-AS1 upregulated the protein levels of ADAM23 but depleted the protein levels of GPX4, SLC3A2, and SLC7A11.

3'-5' RNA helicase YTHDC2

Regulator Info

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[7]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
Cell Process	Cell proliferation
In Vitro Model	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
	BEAS-2B cells	Normal	Homo sapiens	CVCL_0168
	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H1299 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	PC-9 cells	Lung adenocarcinoma	Homo sapiens	CVCL_B260
	NCI-H1975 cells	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	NCI-H441 cells	Lung papillary adenocarcinoma	Homo sapiens	CVCL_1561
	NCI-H1650 cells	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	HCC827 cells	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	NCI-H292 cells	Lung mucoepidermoid carcinoma	Homo sapiens	CVCL_0455
	Calu-1 cells	Lung squamous cell carcinoma	Homo sapiens	CVCL_0608
In Vivo Model	For xenograft experiments, 1.5 x 10⁷ Doxocycline (Dox)-inducible YTHDC2-expressing H1299 cells were subcutaneously injected into 4-6-week-oldathymic nude mice. At day 14 post inoculation, mice were randomly divided into 2 groups for further administrating with or without Dox (30 mg/kg) every other day. Tumors were assessed after sacrificing the mice at day 28 after implantation. Click to Show/Hide
Response Description	The m6A reader YT521-B homology containing 2 (YTHDC2) has been identified to inhibit lung adenocarcinoma (LUAD) tumorigenesis by suppressing solute carrier 7A11 (SLC7A11)-dependent antioxidant function. YTHDC2 also suppresses SLC3A2 subunit via inhibiting HOXA13-mediated SLC3A2 transcription.

Unspecific Regulator

Diabetes mellitus [ICD-11: 5A10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[8]
Responsed Drug	Cryptochlorogenic acid		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	INS-1 cells	Insulinoma	Rattus norvegicus	CVCL_0352
In Vivo Model	Sixty Sprague-Dawley (SD) rats with weights ranging from 250-270 g were obtained from experimental animal center of Xiamen university. For diabetes model group, fasting was performed for 12 h before experiment. The rats (ten rats per group) were assigned into Control group, Model (DM) treated with 50 mg/kg streptozotocin (STZ) via abdominal injection, positive control group and experimental groups. The blood glucose level, which is served as the indicator for the diabetes, was monitored herein. The glucose level after modeling is above 16.7 mmol/l, supporting that the modeling is successful. Click to Show/Hide
Response Description	Cryptochlorogenic acid (CCA) functions via inhibition of ferroptosis by activation of cystine/glutamate transporter system (XC)/glutathione peroxidase 4(GPX4)/Nrf2 and inhibition of nuclear receptor coactivator 4 (NCOA4) in diabetes. System xc- which is composed of SLC7A11 and SLC3A2, served as the provider of GSH synthesis.

Neutrophil gelatinase-associated lipocalin (LCN2)

Regulator Info

Dihydromyricetin [Investigative]

In total 1 item(s) under this drug		Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator		[1]
Regulator for Ferroptosis	Driver
Responsed Disease	Intracerebral hemorrhage [ICD-11: 8B00]	Disease Info
Pathway Response	Fatty acid metabolism	hsa01212
	Ferroptosis	hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	hBCs (Brain cells)
In Vivo Model	Male C57BL/6 mice, aged 8-10 weeks and weighing 22-25 g, were purchased from the Hubei Provincial Center for Disease Control and Prevention in Wuhan, China. Mice were initially administered with 1% sodium pentobarbital (70 mg/kg; Sinopharm Chemical Agent Co., Ltd., Shanghai, China) intraperitoneally. Subsequently, they were secured on a stereotaxic device (RWD Life Science Co., Shenzhen). 0.6 ul of collagenase (1 ku/ml) was injected into the caudate nucleus of the mice (bregma 0: 0.5 mm anterior, 2 mm left lateral and 3.5 mm deep) with the help of a brain stereotactic sampling needle (Hamilton). Click to Show/Hide
Response Description	Dihydromyricetin (DMY) may attenuate symptoms of intracerebral hemorrhage (ICH) in mice, and its potential mechanisms are closely linked to LCN2/system Xc-. The ICH-induced augmentation of LCN2 expression leads to the formation of LCN2-SLC3A2 complexes, which suppress the transport activity of system Xc- and result in the accumulation of ROS and the emergence of ferroptosis.

Bromodomain-containing protein 4 (BRD4)

Regulator Info

JQ1 [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[2]
Regulator for Ferroptosis	Suppressor
Responsed Disease	Breast cancer [ICD-11: 2C60]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Apoptosis			hsa04210
	Autophagy			hsa04140
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell autophagy
	Cell proliferation
	Cell migration
	Cell invasion
In Vitro Model	MDA-MB-231 cells	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	Hs-578T cells	Invasive breast carcinoma	Homo sapiens	CVCL_0332
	NCI-H1299 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	MCF-10A cells	Normal	Homo sapiens	CVCL_0598
In Vivo Model	Female athymic BALB/c nude mice (4-6-week old) were obtained from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). Approximately 1 x 10⁷ cells (A549) in 200 uL of serum-free medium and Matrigel solution were injected directly into the right axilla of each mouse. Tumor growth was measured with calipers every 3 days. Click to Show/Hide
Response Description	Ferroptosis was induced under (+)-JQ1 treatment and BRD4 knockdown, indicating that (+)-JQ1 induces ferroptosis via BRD4 inhibition in breast adenocarcinoma. In addition, expression of the ferroptosis-associated genes GPX4, SLC7A11, and SLC3A2 was downregulated under (+)-JQ1 treatment. Moreover, JQ1 treatment and BRD4 knockdown led to decreased FTH1 expression.

Unspecific Regulator

Cryptochlorogenic acid [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[8]
Responsed Disease	Diabetes mellitus [ICD-11: 5A10]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	INS-1 cells	Insulinoma	Rattus norvegicus	CVCL_0352
In Vivo Model	Sixty Sprague-Dawley (SD) rats with weights ranging from 250-270 g were obtained from experimental animal center of Xiamen university. For diabetes model group, fasting was performed for 12 h before experiment. The rats (ten rats per group) were assigned into Control group, Model (DM) treated with 50 mg/kg streptozotocin (STZ) via abdominal injection, positive control group and experimental groups. The blood glucose level, which is served as the indicator for the diabetes, was monitored herein. The glucose level after modeling is above 16.7 mmol/l, supporting that the modeling is successful. Click to Show/Hide
Response Description	Cryptochlorogenic acid (CCA) functions via inhibition of ferroptosis by activation of cystine/glutamate transporter system (XC)/glutathione peroxidase 4(GPX4)/Nrf2 and inhibition of nuclear receptor coactivator 4 (NCOA4) in diabetes. System xc- which is composed of SLC7A11 and SLC3A2, served as the provider of GSH synthesis.

References

Ref 1	Dihydromyricetin attenuates intracerebral hemorrhage by reversing the effect of LCN2 via the system Xc- pathway. Phytomedicine. 2023 Jul;115:154756. doi: 10.1016/j.phymed.2023.154756. Epub 2023 Mar 12.
Ref 2	Ferritinophagy is required for the induction of ferroptosis by the bromodomain protein BRD4 inhibitor (+)-JQ1 in cancer cells. Cell Death Dis. 2019 Apr 15;10(5):331. doi: 10.1038/s41419-019-1564-7.
Ref 3	Metadherin enhances vulnerability of cancer cells to ferroptosis. Cell Death Dis. 2019 Sep 17;10(10):682. doi: 10.1038/s41419-019-1897-2.
Ref 4	CD8(+) T cells regulate tumour ferroptosis during cancer immunotherapy. Nature. 2019 May;569(7755):270-274. doi: 10.1038/s41586-019-1170-y. Epub 2019 May 1.
Ref 5	Mechanism and Role of the Neuropeptide LGI1 Receptor ADAM23 in Regulating Biomarkers of Ferroptosis and Progression of Esophageal Cancer. Dis Markers. 2021 Dec 30;2021:9227897. doi: 10.1155/2021/9227897. eCollection 2021.
Ref 6	Exosomal miR-142-3p secreted by hepatitis B virus (HBV)-hepatocellular carcinoma (HCC) cells promotes ferroptosis of M1-type macrophages through SLC3A2 and the mechanism of HCC progression. J Gastrointest Oncol. 2022 Apr;13(2):754-767. doi: 10.21037/jgo-21-916.
Ref 7	Targeting SLC3A2 subunit of system X(C)(-) is essential for m(6)A reader YTHDC2 to be an endogenous ferroptosis inducer in lung adenocarcinoma. Free Radic Biol Med. 2021 May 20;168:25-43. doi: 10.1016/j.freeradbiomed.2021.03.023. Epub 2021 Mar 27.
Ref 8	The Protective Effects of Cryptochlorogenic Acid on -Cells Function in Diabetes in vivo and vitro via Inhibition of Ferroptosis. Diabetes Metab Syndr Obes. 2020 Jun 8;13:1921-1931. doi: 10.2147/DMSO.S249382. eCollection 2020.

Ferroptosis Target Information

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Correspondence

Prof. Shuiping Liu