Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10279)
Regulator Name Fibronectin type III domain-containing protein 5 (FNDC5)
Synonyms
FRCP2; Fibronectin type III repeat-containing protein 2
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Gene Name FNDC5
Gene ID 252995
Regulator Type Protein coding
Uniprot ID Q8NAU1
Sequence
MHPGSPSAWPPRARAALRLWLGCVCFALVQADSPSAPVNVTVRHLKANSAVVSWDVLEDE
VVIGFAISQQKKDVRMLRFIQEVNTTTRSCALWDLEEDTEYIVHVQAISIQGQSPASEPV
LFKTPREAEKMASKNKDEVTMKEMGRNQQLRTGEVLIIVVVLFMWAGVIALFCRQYDIIK
DNEPNNNKEKTKSASETSTPEHQGGGLLRSKI

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Function
Contrary to mouse, may not be involved in the beneficial effects of muscular exercise, nor in the induction of browning of human white adipose tissue.

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HGNC ID
HGNC:20240
KEGG ID hsa:252995
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
FNDC5 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
Browse Drug
Nuclear factor erythroid 2-related factor 2 (NFE2L2) [Suppressor; Marker]
 Target Info 
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Acute myocardial infarction ICD-11: BA41
 Disease Info 
Responsed Drug Iridin Investigative
 Drug Info 
Pathway Response Ferroptosis hsa04216
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model
 hCMs (Human cardiomyocytes)
Response regulation Myocardial infarction is characterized by cardiomyocyte death and mitochondrial dysfunction induced by ischemia. FNDC5 overexpression and/or irisin administration elevated cell viability, decreased ferroptosis, and reversed mitochondrial impairments induced by hypoxia. Mechanistically, FNDC5/irisin reduced ferroptosis and reversed mitochondrial impairments by Nrf2/HO-1 axis in hypoxic cardiomyocytes.
Experiment 2 Reporting the Ferroptosis Target of This Regulator [2]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12
 Disease Info 
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process Cell ferroptosis
In Vitro Model
 Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
In Vivo Model
Mice weighing between 20 and 23 g were selected and 5 x 106 Hep-G2 cells were subcutaneously injected into their backs. The mice were subsequently divided into the following four groups: control (n = 5), FNDC5 overexpressing (n = 5), FNDC5 overexpressing followed by treatment with the PI3K inhibitor LY294002 (MCE, China), and FNDC5 knockdown (n = 5). Seven days after cell injection, sorafenib (30 mg/kg) was administered to all mice via intraperitoneal injection every alternate day for 4 weeks. The mice in the third group were intraperitoneally injected with LY294002 (25 mg/kg) diluted with DMSO twice a week for 4 weeks.

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Response regulation FNDC5 activated the PI3K/Akt pathway, which in turn promoted the nuclear translocation of Nrf2 and increased the intracellular antioxidant response in Hepatocellular Carcinoma Cells, thereby conferring resistance to ferroptosis. Our study provides novel insights for improving the efficacy of sorafenib.
Heme oxygenase 1 (HMOX1) [Driver; Suppressor]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Suppressor
Responsed Disease Acute myocardial infarction ICD-11: BA41
 Disease Info 
Responsed Drug Iridin Investigative
 Drug Info 
Pathway Response Ferroptosis hsa04216
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model
 hCMs (Human cardiomyocytes)
Response regulation Myocardial infarction is characterized by cardiomyocyte death and mitochondrial dysfunction induced by ischemia. FNDC5 overexpression and/or irisin administration elevated cell viability, decreased ferroptosis, and reversed mitochondrial impairments induced by hypoxia. Mechanistically, FNDC5/irisin reduced ferroptosis and reversed mitochondrial impairments by Nrf2/HO-1 axis in hypoxic cardiomyocytes.
Acute myocardial infarction [ICD-11: BA41]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Fibronectin type III domain-containing protein 5 (FNDC5) Protein coding
 Regulator Info 
Responsed Drug Iridin Investigative
 Drug Info 
Pathway Response Ferroptosis hsa04216
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model
 hCMs (Human cardiomyocytes)
Response regulation Myocardial infarction is characterized by cardiomyocyte death and mitochondrial dysfunction induced by ischemia. FNDC5 overexpression and/or irisin administration elevated cell viability, decreased ferroptosis, and reversed mitochondrial impairments induced by hypoxia. Mechanistically, FNDC5/irisin reduced ferroptosis and reversed mitochondrial impairments by Nrf2/HO-1 axis in hypoxic cardiomyocytes.
Experiment 2 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Fibronectin type III domain-containing protein 5 (FNDC5) Protein coding
 Regulator Info 
Responsed Drug Iridin Investigative
 Drug Info 
Pathway Response Ferroptosis hsa04216
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model
 hCMs (Human cardiomyocytes)
Response regulation Myocardial infarction is characterized by cardiomyocyte death and mitochondrial dysfunction induced by ischemia. FNDC5 overexpression and/or irisin administration elevated cell viability, decreased ferroptosis, and reversed mitochondrial impairments induced by hypoxia. Mechanistically, FNDC5/irisin reduced ferroptosis and reversed mitochondrial impairments by Nrf2/HO-1 axis in hypoxic cardiomyocytes.
Hepatocellular carcinoma [ICD-11: 2C12]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Fibronectin type III domain-containing protein 5 (FNDC5) Protein coding
 Regulator Info 
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process Cell ferroptosis
In Vitro Model
 Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
In Vivo Model
Mice weighing between 20 and 23 g were selected and 5 x 106 Hep-G2 cells were subcutaneously injected into their backs. The mice were subsequently divided into the following four groups: control (n = 5), FNDC5 overexpressing (n = 5), FNDC5 overexpressing followed by treatment with the PI3K inhibitor LY294002 (MCE, China), and FNDC5 knockdown (n = 5). Seven days after cell injection, sorafenib (30 mg/kg) was administered to all mice via intraperitoneal injection every alternate day for 4 weeks. The mice in the third group were intraperitoneally injected with LY294002 (25 mg/kg) diluted with DMSO twice a week for 4 weeks.

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Response regulation FNDC5 activated the PI3K/Akt pathway, which in turn promoted the nuclear translocation of Nrf2 and increased the intracellular antioxidant response in Hepatocellular Carcinoma Cells, thereby conferring resistance to ferroptosis. Our study provides novel insights for improving the efficacy of sorafenib.
Iridin [Investigative]
 Drug Info 
In total 2 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Suppressor
Response Target Nuclear factor erythroid 2-related factor 2 (NFE2L2) Suppressor; Marker
 Target Info 
Responsed Disease Acute myocardial infarction ICD-11: BA41
 Disease Info 
Pathway Response Ferroptosis hsa04216
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model
 hCMs (Human cardiomyocytes)
Response regulation Myocardial infarction is characterized by cardiomyocyte death and mitochondrial dysfunction induced by ischemia. FNDC5 overexpression and/or irisin administration elevated cell viability, decreased ferroptosis, and reversed mitochondrial impairments induced by hypoxia. Mechanistically, FNDC5/irisin reduced ferroptosis and reversed mitochondrial impairments by Nrf2/HO-1 axis in hypoxic cardiomyocytes.
Experiment 2 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Suppressor
Response Target Heme oxygenase 1 (HMOX1) Driver; Suppressor
 Target Info 
Responsed Disease Acute myocardial infarction ICD-11: BA41
 Disease Info 
Pathway Response Ferroptosis hsa04216
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model
 hCMs (Human cardiomyocytes)
Response regulation Myocardial infarction is characterized by cardiomyocyte death and mitochondrial dysfunction induced by ischemia. FNDC5 overexpression and/or irisin administration elevated cell viability, decreased ferroptosis, and reversed mitochondrial impairments induced by hypoxia. Mechanistically, FNDC5/irisin reduced ferroptosis and reversed mitochondrial impairments by Nrf2/HO-1 axis in hypoxic cardiomyocytes.
References
Ref 1 FNDC5/irisin reduces ferroptosis and improves mitochondrial dysfunction in hypoxic cardiomyocytes by Nrf2/HO-1 axis. Cell Biol Int. 2022 May;46(5):723-736. doi: 10.1002/cbin.11763. Epub 2022 Jan 23.
Ref 2 FNDC5 Causes Resistance to Sorafenib by Activating the PI3K/Akt/Nrf2 Pathway in Hepatocellular Carcinoma Cells. Front Oncol. 2022 Mar 22;12:852095. doi: 10.3389/fonc.2022.852095. eCollection 2022.