Ferroptosis Regulator Information
General Information of the Ferroptosis Regulator (ID: REG20014)
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
hsa-miR-7-5p
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).
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Transferrin receptor protein 1 (TFRC) [Driver; Suppressor; Marker]
In total 2 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis Target of This Regulator | [1] | ||||
Target for Ferroptosis | Marker/Suppressor/Driver | ||||
Responsed Disease | Cardiomyopathy | ICD-11: BC43 | |||
Responsed Drug | Doxorubicin | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model |
AC16 [Human hybrid cardiomyocyte] cells | Normal | Homo sapiens | CVCL_4U18 | |
In Vivo Model |
Male Sprague-Dawley rats (6-8 weeks old; weighed from 210 to 230 g) were purchased from HFK Bioscience Co. Ltd. Rats were randomly assigned to four groups (n = 6 per group). The first was the control group, which were treated daily with 0.5 ml of 0.9% saline by intraperitoneal injection for 14 days, and there were three DOX model groups, which were treated three times weekly with 2.5 mg/kg of DOX by intraperitoneal injection for 14 weeks. At day 14, mice in the DOX model groups were infected through an intramyocardial injection of either control shNC or shMettl14 (1 x 109 titer) at three distinct locations in the left ventricular free wall three times a week for 2 weeks, and they were treated daily with 30 mg/kg of ferroptosis inducer erastin (MedChemExpress, USA) through intragastric administration or vehicle control (Saline) for 2 weeks.
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Response regulation | Doxorubicin treatment resulted in the upregulation of methyltransferase-like 14 (METTL14), which catalyzes the m6A modification of the long non-coding RNA KCNQ1OT1, a miR-7-5p sponge. And miR-7-5p inhibits DOX-induced ferroptosis in cardiomyocytes by directly repressing TFRC. Inhibiting ferroptosis mediated by a METTL14/KCNQ1OT1/miR-7-5p positive feedback loop in cardiomyocytes could provide a new therapeutic approach to control DOX-induced cardiac injury. | ||||
Experiment 2 Reporting the Ferroptosis Target of This Regulator | [1] | ||||
Target for Ferroptosis | Marker/Suppressor/Driver | ||||
Responsed Disease | Cardiomyopathy | ICD-11: BC43 | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model |
AC16 [Human hybrid cardiomyocyte] cells | Normal | Homo sapiens | CVCL_4U18 | |
In Vivo Model |
Male Sprague-Dawley rats (6-8 weeks old; weighed from 210 to 230 g) were purchased from HFK Bioscience Co. Ltd. Rats were randomly assigned to four groups (n = 6 per group). The first was the control group, which were treated daily with 0.5 ml of 0.9% saline by intraperitoneal injection for 14 days, and there were three DOX model groups, which were treated three times weekly with 2.5 mg/kg of DOX by intraperitoneal injection for 14 weeks. At day 14, mice in the DOX model groups were infected through an intramyocardial injection of either control shNC or shMettl14 (1 x 109 titer) at three distinct locations in the left ventricular free wall three times a week for 2 weeks, and they were treated daily with 30 mg/kg of ferroptosis inducer erastin (MedChemExpress, USA) through intragastric administration or vehicle control (Saline) for 2 weeks.
Click to Show/Hide
|
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Response regulation | The RNA-binding protein IGF2BP1 is associated with KCNQ1OT1 to increase its stability and robustly inhibit miR-7-5p activity. MiR-7-5p could effectively suppress METLL14 and TFRC expression. The study suggested a therapeutic strategy to alleviate doxorubicin (DOX)-induced cardiomyopathy. | ||||
Polyunsaturated fatty acid lipoxygenase ALOX12 (ALOX12) [Driver]
In total 1 item(s) under this target | ||||
Experiment 1 Reporting the Ferroptosis Target of This Regulator | [2] | |||
Target for Ferroptosis | Driver | |||
Responsed Disease | Cervical cancer | ICD-11: 2C77 | ||
Pathway Response | Fatty acid metabolism | hsa01212 | ||
Cell Process | Cell ferroptosis | |||
In Vitro Model |
HeLa cells | Endocervical adenocarcinoma | Homo sapiens | CVCL_0030 |
SAS cells | Tongue squamous cell carcinoma | Homo sapiens | CVCL_1675 | |
Response regulation | Knockdown of miR-7-5p increased reactive oxygen species (ROS), mitochondrial membrane potential, and intracellular Fe2+amount. Furthermore, miR-7-5p knockdown results in the down-regulation of the iron storage gene expression such as ferritin, up-regulation of the ferroptosis marker ALOX12 gene expression, and increases of Liperfluo amount in Endocervical adenocarcinoma. | |||
Long-chain-fatty-acid--CoA ligase 4 (ACSL4) [Driver]
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis Target of This Regulator | [3] | ||||
Target for Ferroptosis | Driver | ||||
Responsed Disease | Retinopathy | ICD-11: 9B71 | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model |
hRECs (Human retinal endothelial cells) | ||||
In Vivo Model |
For in vivo experiments, the eyes in each group (n = 6) were enucleated carefully and processed for indirect immunofluorescence in whole-mount or cross-section as previously described. For cryosections, the eyes (n = 3 retinae from 3 mice) were fixed in 4% PFA at room temperature for 15 min. The frozen samples were then sliced transversely (6 um) at -20. For retinal flat-mounts, the eyes (n = 3 eyes from 3 mice) were fixed in 4% PFA at room temperature for 15 min, and the retinae were dissected out as cups. Both cryosections and retinal cups were blocked with PBS containing 0.5% Triton-X100 and 5% BSA at 4 overnight and included with the anti-CD31 and anti-GPX4 (1:100, ab125066, Abcam) primary antibodies.
Click to Show/Hide
|
||||
Response regulation | ZFAS1 may act as a competing endogenous RNA by competitively binding with microRNA-7-5p (miR-7-5p) and modulating the expression of its downstream molecule acyl-CoA synthetase long-chain family member 4 (ACSL4), which is now identified as a classic driver gene of ferroptosis process. In conclusion, our results demonstrate that HG-induced ZFAS1 elevation activates ferroptosis in hRECs and the ZFAS1/ miR-7-5p/ACSL4 axis may serve as a therapeutic target for endothelial dysfunction in diabetic retinopathy. | ||||
Cardiomyopathy [ICD-11: BC43]
In total 2 item(s) under this disease | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response | [1] | ||||
Target Regulator | hsa-miR-7-5p (miRNA) | miRNA | |||
Responsed Drug | Doxorubicin | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model |
AC16 [Human hybrid cardiomyocyte] cells | Normal | Homo sapiens | CVCL_4U18 | |
In Vivo Model |
Male Sprague-Dawley rats (6-8 weeks old; weighed from 210 to 230 g) were purchased from HFK Bioscience Co. Ltd. Rats were randomly assigned to four groups (n = 6 per group). The first was the control group, which were treated daily with 0.5 ml of 0.9% saline by intraperitoneal injection for 14 days, and there were three DOX model groups, which were treated three times weekly with 2.5 mg/kg of DOX by intraperitoneal injection for 14 weeks. At day 14, mice in the DOX model groups were infected through an intramyocardial injection of either control shNC or shMettl14 (1 x 109 titer) at three distinct locations in the left ventricular free wall three times a week for 2 weeks, and they were treated daily with 30 mg/kg of ferroptosis inducer erastin (MedChemExpress, USA) through intragastric administration or vehicle control (Saline) for 2 weeks.
Click to Show/Hide
|
||||
Response regulation | Doxorubicin treatment resulted in the upregulation of methyltransferase-like 14 (METTL14), which catalyzes the m6A modification of the long non-coding RNA KCNQ1OT1, a miR-7-5p sponge. And miR-7-5p inhibits DOX-induced ferroptosis in cardiomyocytes by directly repressing TFRC. Inhibiting ferroptosis mediated by a METTL14/KCNQ1OT1/miR-7-5p positive feedback loop in cardiomyocytes could provide a new therapeutic approach to control DOX-induced cardiac injury. | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response | [1] | ||||
Target Regulator | hsa-miR-7-5p (miRNA) | miRNA | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model |
AC16 [Human hybrid cardiomyocyte] cells | Normal | Homo sapiens | CVCL_4U18 | |
In Vivo Model |
Male Sprague-Dawley rats (6-8 weeks old; weighed from 210 to 230 g) were purchased from HFK Bioscience Co. Ltd. Rats were randomly assigned to four groups (n = 6 per group). The first was the control group, which were treated daily with 0.5 ml of 0.9% saline by intraperitoneal injection for 14 days, and there were three DOX model groups, which were treated three times weekly with 2.5 mg/kg of DOX by intraperitoneal injection for 14 weeks. At day 14, mice in the DOX model groups were infected through an intramyocardial injection of either control shNC or shMettl14 (1 x 109 titer) at three distinct locations in the left ventricular free wall three times a week for 2 weeks, and they were treated daily with 30 mg/kg of ferroptosis inducer erastin (MedChemExpress, USA) through intragastric administration or vehicle control (Saline) for 2 weeks.
Click to Show/Hide
|
||||
Response regulation | The RNA-binding protein IGF2BP1 is associated with KCNQ1OT1 to increase its stability and robustly inhibit miR-7-5p activity. MiR-7-5p could effectively suppress METLL14 and TFRC expression. The study suggested a therapeutic strategy to alleviate doxorubicin (DOX)-induced cardiomyopathy. | ||||
Cervical cancer [ICD-11: 2C77]
In total 1 item(s) under this disease | ||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response | [2] | |||
Target Regulator | hsa-miR-7-5p (miRNA) | miRNA | ||
Pathway Response | Fatty acid metabolism | hsa01212 | ||
Cell Process | Cell ferroptosis | |||
In Vitro Model |
HeLa cells | Endocervical adenocarcinoma | Homo sapiens | CVCL_0030 |
SAS cells | Tongue squamous cell carcinoma | Homo sapiens | CVCL_1675 | |
Response regulation | Knockdown of miR-7-5p increased reactive oxygen species (ROS), mitochondrial membrane potential, and intracellular Fe2+amount. Furthermore, miR-7-5p knockdown results in the down-regulation of the iron storage gene expression such as ferritin, up-regulation of the ferroptosis marker ALOX12 gene expression, and increases of Liperfluo amount in Endocervical adenocarcinoma. | |||
Retinopathy [ICD-11: 9B71]
In total 1 item(s) under this disease | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response | [3] | ||||
Target Regulator | hsa-miR-7-5p (miRNA) | miRNA | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model |
hRECs (Human retinal endothelial cells) | ||||
In Vivo Model |
For in vivo experiments, the eyes in each group (n = 6) were enucleated carefully and processed for indirect immunofluorescence in whole-mount or cross-section as previously described. For cryosections, the eyes (n = 3 retinae from 3 mice) were fixed in 4% PFA at room temperature for 15 min. The frozen samples were then sliced transversely (6 um) at -20. For retinal flat-mounts, the eyes (n = 3 eyes from 3 mice) were fixed in 4% PFA at room temperature for 15 min, and the retinae were dissected out as cups. Both cryosections and retinal cups were blocked with PBS containing 0.5% Triton-X100 and 5% BSA at 4 overnight and included with the anti-CD31 and anti-GPX4 (1:100, ab125066, Abcam) primary antibodies.
Click to Show/Hide
|
||||
Response regulation | ZFAS1 may act as a competing endogenous RNA by competitively binding with microRNA-7-5p (miR-7-5p) and modulating the expression of its downstream molecule acyl-CoA synthetase long-chain family member 4 (ACSL4), which is now identified as a classic driver gene of ferroptosis process. In conclusion, our results demonstrate that HG-induced ZFAS1 elevation activates ferroptosis in hRECs and the ZFAS1/ miR-7-5p/ACSL4 axis may serve as a therapeutic target for endothelial dysfunction in diabetic retinopathy. | ||||
Doxorubicin
[Investigative]
In total 1 item(s) under this drug | |||||
Experiment 1 Reporting the Ferroptosis-centered Drug Response | [1] | ||||
Drug for Ferroptosis | Inducer | ||||
Response Target | Transferrin receptor protein 1 (TFRC) | Driver; Suppressor; Marker | |||
Responsed Disease | Cardiomyopathy | ICD-11: BC43 | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model |
AC16 [Human hybrid cardiomyocyte] cells | Normal | Homo sapiens | CVCL_4U18 | |
In Vivo Model |
Male Sprague-Dawley rats (6-8 weeks old; weighed from 210 to 230 g) were purchased from HFK Bioscience Co. Ltd. Rats were randomly assigned to four groups (n = 6 per group). The first was the control group, which were treated daily with 0.5 ml of 0.9% saline by intraperitoneal injection for 14 days, and there were three DOX model groups, which were treated three times weekly with 2.5 mg/kg of DOX by intraperitoneal injection for 14 weeks. At day 14, mice in the DOX model groups were infected through an intramyocardial injection of either control shNC or shMettl14 (1 x 109 titer) at three distinct locations in the left ventricular free wall three times a week for 2 weeks, and they were treated daily with 30 mg/kg of ferroptosis inducer erastin (MedChemExpress, USA) through intragastric administration or vehicle control (Saline) for 2 weeks.
Click to Show/Hide
|
||||
Response regulation | Doxorubicin treatment resulted in the upregulation of methyltransferase-like 14 (METTL14), which catalyzes the m6A modification of the long non-coding RNA KCNQ1OT1, a miR-7-5p sponge. And miR-7-5p inhibits DOX-induced ferroptosis in cardiomyocytes by directly repressing TFRC. Inhibiting ferroptosis mediated by a METTL14/KCNQ1OT1/miR-7-5p positive feedback loop in cardiomyocytes could provide a new therapeutic approach to control DOX-induced cardiac injury. | ||||
References