Ferroptosis-centered Disease Response Information

General Information of the Disease (ID: DIS00041)
Name
Corpus uteri cancer
ICD
ICD-11: 2C76
Full List of Target(s) of This Ferroptosis-centered Disease
Solute carrier family 40 member 1 (SLC40A1)
 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 Corpus uteri cancer [ICD-11: 2C76]
Responsed Drug Simvastatin Investigative
 Drug Info 
Responsed Regulator Mitogen-activated protein kinase 1 (MAPK1) Suppressor
 Regulator Info 
Pathway Response MAPK signaling pathway hsa04010
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model Ishikawa cells Endometrial adenocarcinoma Homo sapiens CVCL_2529
Response regulation Simvastatin has the potential to be a targeted drug for endometrial cancer (EC) treatment. Besides, the inhibition to the RAS/MAPK signaling pathway allows simvastatin to induce ferroptosis through up-regulating the level of ROS, MDA, Fe2+, and TRF1 (TF) and reducing the level of GSH, SLC7A11, and FPN in cells.
Serotransferrin (TF)
 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/Driver
Responsed Disease Corpus uteri cancer [ICD-11: 2C76]
Responsed Drug Simvastatin Investigative
 Drug Info 
Responsed Regulator Mitogen-activated protein kinase 1 (MAPK1) Suppressor
 Regulator Info 
Pathway Response MAPK signaling pathway hsa04010
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model Ishikawa cells Endometrial adenocarcinoma Homo sapiens CVCL_2529
Response regulation Simvastatin has the potential to be a targeted drug for endometrial cancer (EC) treatment. Besides, the inhibition to the RAS/MAPK signaling pathway allows simvastatin to induce ferroptosis through up-regulating the level of ROS, MDA, Fe2+, and TRF1 (TF) and reducing the level of GSH, SLC7A11, and FPN in cells.
Cystine/glutamate transporter (SLC7A11)
 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 Corpus uteri cancer [ICD-11: 2C76]
Responsed Drug Simvastatin Investigative
 Drug Info 
Responsed Regulator Mitogen-activated protein kinase 1 (MAPK1) Suppressor
 Regulator Info 
Pathway Response MAPK signaling pathway hsa04010
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model Ishikawa cells Endometrial adenocarcinoma Homo sapiens CVCL_2529
Response regulation Simvastatin has the potential to be a targeted drug for endometrial cancer (EC) treatment. Besides, the inhibition to the RAS/MAPK signaling pathway allows simvastatin to induce ferroptosis through up-regulating the level of ROS, MDA, Fe2+, and TRF1 (TF) and reducing the level of GSH, SLC7A11, and FPN in cells.
Unspecific Target
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Responsed Disease Corpus uteri cancer [ICD-11: 2C76]
Responsed Drug Amentoflavone Investigative
 Drug Info 
Responsed Regulator Serine/threonine-protein kinase mTOR (MTOR) Suppressor
 Regulator Info 
Pathway Response mTOR signaling pathway hsa04150
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
In Vitro Model hESCs (Human endometrial stromal cells)
KLE cells Endometrial adenocarcinoma Homo sapiens CVCL_1329
Response regulation Amentoflavone inhibited the viability and proliferation of endometrial carcinoma cells (KLE) cells but promoted apoptosis and ferroptosis. The expressions of ROS and AMPK were increased, while mTOR expression was decreased in AF-treated KLE cells. NAC reversed the effects of AF on biological behaviors of KLE cells by inactivating ROS/AMPK/mTOR signaling.
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Responsed Disease Corpus uteri cancer [ICD-11: 2C76]
Responsed Drug Amentoflavone Investigative
 Drug Info 
Responsed Regulator 5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1) Driver
 Regulator Info 
Pathway Response mTOR signaling pathway hsa04150
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
In Vitro Model hESCs (Human endometrial stromal cells)
KLE cells Endometrial adenocarcinoma Homo sapiens CVCL_1329
Response regulation Amentoflavone inhibited the viability and proliferation of endometrial carcinoma cells (KLE) cells but promoted apoptosis and ferroptosis. The expressions of ROS and AMPK were increased, while mTOR expression was decreased in AF-treated KLE cells. NAC reversed the effects of AF on biological behaviors of KLE cells by inactivating ROS/AMPK/mTOR signaling.
Transferrin receptor protein 1 (TFRC)
 Target Info 
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [3]
Target for Ferroptosis Marker/Suppressor/Driver
Responsed Disease Corpus uteri cancer [ICD-11: 2C76]
Responsed Regulator CircRAPGEF5 (circRNA) Suppressor
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model KLE cells Endometrial adenocarcinoma Homo sapiens CVCL_1329
Ishikawa cells Endometrial adenocarcinoma Homo sapiens CVCL_2529
HEC-1-A cells Endometrial adenocarcinoma Homo sapiens CVCL_0293
HEC-1-B cells Endometrial adenocarcinoma Homo sapiens CVCL_0294
RL95-2 cells Endometrial adenosquamous carcinoma Homo sapiens CVCL_0505
In Vivo Model
Female 4-week-old BALB/c-nu nude mice were purchased from Vital River (Beijing, China) and housed in a specific pathogen-free facility. EC cells were washed twice with serum-free medium and injected subcutaneously into nude mice (5 x 106 cells/site). Tumors were measured with calipers every four days for four weeks. The mice were sacrificed on day 32 after cell implantation, and the tumors were excised and weighed.

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Response regulation CircRAPGEF5 interacts with RBFOX2, an important splicing regulator, to modulate the splicing of TFRC pre-mRNA. Importantly, circRAPGEF5 promotes exon-4 skipping of TFRC by sequestering RBFOX2, resulting in resistance to ferroptosis via the reduction of labile iron in endometrial cancer cells.
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [3]
Target for Ferroptosis Marker/Suppressor/Driver
Responsed Disease Corpus uteri cancer [ICD-11: 2C76]
Responsed Regulator RNA binding protein fox-1 homolog 2 (RBFOX2) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model KLE cells Endometrial adenocarcinoma Homo sapiens CVCL_1329
Ishikawa cells Endometrial adenocarcinoma Homo sapiens CVCL_2529
HEC-1-A cells Endometrial adenocarcinoma Homo sapiens CVCL_0293
HEC-1-B cells Endometrial adenocarcinoma Homo sapiens CVCL_0294
RL95-2 cells Endometrial adenosquamous carcinoma Homo sapiens CVCL_0505
In Vivo Model
Female 4-week-old BALB/c-nu nude mice were purchased from Vital River (Beijing, China) and housed in a specific pathogen-free facility. EC cells were washed twice with serum-free medium and injected subcutaneously into nude mice (5 x 106 cells/site). Tumors were measured with calipers every four days for four weeks. The mice were sacrificed on day 32 after cell implantation, and the tumors were excised and weighed.

    Click to Show/Hide
Response regulation CircRAPGEF5 interacts with RBFOX2, an important splicing regulator, to modulate the splicing of TFRC pre-mRNA. Importantly, circRAPGEF5 promotes exon-4 skipping of TFRC by sequestering RBFOX2, resulting in resistance to ferroptosis via the reduction of labile iron in endometrial cancer cells.
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
 Target Info 
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [4]
Target for Ferroptosis Suppressor
Responsed Disease Corpus uteri cancer [ICD-11: 2C76]
Responsed Regulator Tyrosine-protein phosphatase non-receptor type 18 (PTPN18) Suppressor
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model KLE cells Endometrial adenocarcinoma Homo sapiens CVCL_1329
Response regulation Silencing of PTPN18 induced ferroptosis in KLE endometrial cancer cells. PTPN18 knockdown increased intracellular ROS level and down-regulated GPX4 and xCT expression. Besides, silencing of PTPN18 also induced the expression of p-p38 (MAPK14).
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [4]
Target for Ferroptosis Suppressor
Responsed Disease Corpus uteri cancer [ICD-11: 2C76]
Responsed Regulator Mitogen-activated protein kinase 14 (MAPK14) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model KLE cells Endometrial adenocarcinoma Homo sapiens CVCL_1329
Response regulation Silencing of PTPN18 induced ferroptosis in KLE endometrial cancer cells. PTPN18 knockdown increased intracellular ROS level and down-regulated GPX4 and xCT expression. Besides, silencing of PTPN18 also induced the expression of p-p38 (MAPK14).
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 [5]
Target for Ferroptosis Driver/Suppressor
Responsed Disease Corpus uteri cancer [ICD-11: 2C76]
Responsed Drug Juglone Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
Cell migration
In Vitro Model Ishikawa cells Endometrial adenocarcinoma Homo sapiens CVCL_2529
Response regulation Juglone as a natural quinone from C. cathayensisgreen peel could exert its anti-cancer activity by inducing iron dependent autophagy and inhibiting the migration of endometrial cancer (EC) cells. Subsequently, Fe2+ accumulation, lipid peroxidation, GSH depletion, the upregulation of HMOX1, and heme degradation to Fe2+ were reported. Juglone was involved in inducing autophagy and inhibiting cell migration and endoplasmic reticulum stress.
References
Ref 1 Simvastatin Inhibits Endometrial Cancer Malignant Behaviors by Suppressing RAS/Mitogen-Activated Protein Kinase (MAPK) Pathway-Mediated Reactive Oxygen Species (ROS) and Ferroptosis. Evid Based Complement Alternat Med. 2022 Oct 14;2022:6177477. doi: 10.1155/2022/6177477. eCollection 2022.
Ref 2 Amentoflavone promotes ferroptosis by regulating reactive oxygen species (ROS) /5'AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) to inhibit the malignant progression of endometrial carcinoma cells. Bioengineered. 2022 May;13(5):13269-13279. doi: 10.1080/21655979.2022.2079256.
Ref 3 CircRAPGEF5 interacts with RBFOX2 to confer ferroptosis resistance by modulating alternative splicing of TFRC in endometrial cancer. Redox Biol. 2022 Sep 26;57:102493. doi: 10.1016/j.redox.2022.102493. Online ahead of print.
Ref 4 Silencing of PTPN18 Induced Ferroptosis in Endometrial Cancer Cells Through p-P38-Mediated GPX4/xCT Down-Regulation. Cancer Manag Res. 2021 Feb 19;13:1757-1765. doi: 10.2147/CMAR.S278728. eCollection 2021.
Ref 5 Juglone, a novel activator of ferroptosis, induces cell death in endometrial carcinoma Ishikawa cells. Food Funct. 2021 Jun 8;12(11):4947-4959. doi: 10.1039/d1fo00790d.